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Gene Information
Gene symbol: APLP2
Gene name: amyloid beta (A4) precursor-like protein 2
HGNC ID: 598
Synonyms: APPH
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1212427 | The reduced incidence of amyloidosis following BAPN adminsitration cannot be due to lysosomal enzyme degradation of the amyloid as the activity of cathepsin D and acid phosphatase is decreased during this process. |
| 2 | 3092598 | Furthermore, levels of serum amyloid P component (SAP) were also determined. |
| 3 | 8213351 | Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. |
| 4 | 8213351 | A simple and reliable animal model to quantify interleukin-1 (IL-1) production at a site of inflammation has been developed and characterised. |
| 5 | 8213351 | The local inflammatory reaction in the chamber, over a 30 day time course, was characterised by leucocyte infiltration, and marked increases in protein, prostaglandin E2, IL-1 and IL-6 concentrations in the chamber fluid. |
| 6 | 8213351 | A rapid increase in plasma concentrations of the acute-phase reactant serum amyloid P (SAP) also occurred. |
| 7 | 8382582 | The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. |
| 8 | 8382582 | C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. |
| 9 | 8382582 | Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. |
| 10 | 8382582 | The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. |
| 11 | 8382582 | The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. |
| 12 | 8382582 | C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. |
| 13 | 8382582 | Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. |
| 14 | 8382582 | The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. |
| 15 | 8382582 | The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. |
| 16 | 8382582 | C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. |
| 17 | 8382582 | Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. |
| 18 | 8382582 | The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. |
| 19 | 8382582 | The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. |
| 20 | 8382582 | C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. |
| 21 | 8382582 | Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. |
| 22 | 8382582 | The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. |
| 23 | 9548303 | Typhoid vaccination increased levels of SAA, haptoglobin alpha1, haptoglobin alpha2, haptoglobin beta and alpha1-anti-chymotrypsin but decreased transthyretin and apolipoprotein E. |
| 24 | 9548303 | In RA patients, serum amyloid A (SAA), haptoglobin alpha2, haptoglobin beta, alpha1-antichymotrypsin and C3 proactivator levels were elevated while apolipoprotein A-I, apolipoprotein A-IV, transthyretin, Gc-globulin, alpha2-HS glycoprotein, alpha2-macroglobulin and alpha1-B glycoprotein levels were decreased, compared to normals. |
| 25 | 9548303 | Compared to piroxicam, tenidap lowered levels of alpha1-antiprotease and SAA but raised the levels of transthyretin, Gc-globulin, alpha2-HS-glycoprotein and alpha2-macroglobulin in RA patients. |
| 26 | 11135604 | Studies in three different transgenic mouse models suggest that the amyloid beta-protein contributes to memory loss in Alzheimer disease. |
| 27 | 11250006 | In Alzheimer's disease (AD), self-aggregation of Abeta becomes rampant, manifested most strikingly as the amyloid fibrils of senile plaques. |
| 28 | 11578774 | The lessons learned from these models are of great interest not only for understanding of the role of TGF-beta in AD, but also for future treatments where testing of anti-inflammatory agents such as ibuprofen and an amyloid vaccine hold great promise. |
| 29 | 11701763 | In recent studies of transgenic models of Alzheimer's disease (AD), it has been reported that antibodies to aged beta amyloid peptide 1-42 (Abeta(1-42)) solutions (mixtures of Abeta monomers, oligomers and amyloid fibrils) cause conspicuous reduction of amyloid plaques and neurological improvement. |
| 30 | 11711855 | Current studies involve administering the amyloid beta peptide (Abeta) in Freund's complete adjuvant, which cannot be used in humans. |
| 31 | 11788049 | Immunization with the Abeta 1-42 peptide has been reported to decrease Abeta deposits in the brains of mutant amyloid precursor protein (APP/V717F) transgenic (tg) mice (Schenk et al. |
| 32 | 11788050 | Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), which is formed from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta in regions of the brain important for memory and cognition. |
| 33 | 11788050 | Our group has demonstrated that vaccination of a doubly transgenic mouse model (expressing mutant APP and presenilin-1) with the Abeta 1-42 peptide protects these mice from the memory deficits they would ordinarily develop. |
| 34 | 11851323 | Here we report the development of a novel immunization procedure to raise effective anti-aggregating amyloid beta-protein (AbetaP) antibodies, using as antigen filamentous phages displaying the only EFRH peptide found to be the epitope of these antibodies. |
| 35 | 12086704 | Active immunization with the human amyloid peptide (Abeta42) or passive immunization with anti-Abeta42 antibodies protects mice that express a mutant human amyloid precursor protein (APP) transgene from cerebral amyloid deposits. |
| 36 | 12177805 | Twelve tumour antigens encoded by known genes were isolated, including ribosomal protein S18, heat shock protein 90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding protein 7, TG-interacting factor, eukaryotic translation initiation factor p40 subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8, CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3. |
| 37 | 12196140 | In Alzheimer's disease, amyloid deposition in the form of neuritic plaques and congophilic angiopathy is driven by the conversion of normal soluble amyloid-beta peptide (sA beta) to A beta plaques; while in the prionoses the critical event is the conversion of normal prion protein, PrP(C), to the disease-associated form, PrP(Sc). |
| 38 | 12230303 | Some cases of AD are caused by mutations in presenilin-1 (PS1), and it has been shown that PS1 mutations perturb neuronal calcium homeostasis, promote increased production of amyloid beta-peptide (Abeta), and render neurons vulnerable to synaptic dysfunction, excitotoxicity, and apoptosis. |
| 39 | 12230303 | LPS-induced levels of mRNAs encoding tumor necrosis fctor-alpha (TNFalpha), interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, and IL-6 are significantly greater in the hippocampus and cerebral cortex of PS1 mutant mice as compared to wild-type mice. |
| 40 | 12230303 | Studies of cultured microglia from PS1 mutant and wild-type mice reveal that PS1 is expressed in microglia and that the PS1 mutation confers a heightened sensitivity to LPS, as indicated by superinduction of inducible nitric oxide synthase (NOS) and activation of mitogen-activated protein kinase (MAPK). |
| 41 | 12235837 | Deposition of amyloid beta protein (A beta) as senile plaques or cerebrovascular amyloid characterizes the brains of patients with Alzheimer's disease (AD). |
| 42 | 12235837 | PS1 and PS2 are shown to be the catalytic subunits of gamma-secretase that cleaves the intramembrane segments of beta APP and Notch. beta-amyloid hypothesis that emphasizes the primacy of A beta in the pathogenesis of AD is currently being verified by the new experimental therapeutic approaches, e.g., A beta vaccine therapy or administration of inhibitors of beta- or gamma-secretases. |
| 43 | 12392768 | Concern over the amyloid vaccine: amyloid heterogeneity and Fc receptor signaling. |
| 44 | 12450704 | Previous studies have shown that in various mouse models of Alzheimer's disease (AD), amyloid beta-protein (Abeta) antibodies generated by Abeta peptide immunization resulted in the prevention of Abeta plaque formation in brains of young mice, decreased Abeta plaque burdens in older mice and improved cognition. |
| 45 | 12470800 | Certain amyloid-binding molecules, such as Congo red (CR) and chrysamine G (CG) and Thioflavin S (TS) have been shown to bind SPs with high affinity and they can also arrest the formation of Abeta fibrils; however, CR, CG and TS are unsuitable for AD therapy because they do not cross the blood brain barrier (BBB). |
| 46 | 12470795 | Although the site of action of the anti-Abeta antibodies has been suggested to be within the brain, peripheral clearance of Abeta may have a greater role in reducing cerebral amyloid plaques in these animals and eventually in AD patients. |
| 47 | 12559780 | The EFRH phage evoked effective auto-immune antibodies in amyloid precursor protein [V717I] (APP[V717I]) transgenic mice that recapitulate the amyloid plaques and vascular pathology of Alzheimer's disease (AD). |
| 48 | 12559780 | The immunization provoked a considerable reduction in the number of Abeta amyloid plaques in the brain of the transgenic mice and may serve as the basis for anti-Abeta vaccine. |
| 49 | 12559780 | The EFRH phage evoked effective auto-immune antibodies in amyloid precursor protein [V717I] (APP[V717I]) transgenic mice that recapitulate the amyloid plaques and vascular pathology of Alzheimer's disease (AD). |
| 50 | 12559780 | The immunization provoked a considerable reduction in the number of Abeta amyloid plaques in the brain of the transgenic mice and may serve as the basis for anti-Abeta vaccine. |
| 51 | 12625030 | Neuritic plaques composed of amyloid beta-protein (A beta) are an early and invariant neuropathological feature of Alzheimer's disease (AD). |
| 52 | 12640446 | Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages. |
| 53 | 12665674 | Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development. |
| 54 | 12665674 | Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer s disease (AD) was halted as the result of serious neurological complications in some patients. |
| 55 | 12665674 | Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. |
| 56 | 12665674 | Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development. |
| 57 | 12665674 | Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer s disease (AD) was halted as the result of serious neurological complications in some patients. |
| 58 | 12665674 | Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. |
| 59 | 12665674 | Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development. |
| 60 | 12665674 | Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer s disease (AD) was halted as the result of serious neurological complications in some patients. |
| 61 | 12665674 | Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. |
| 62 | 12736345 | Active immunization against the beta-amyloid peptide (Alphabeta) with vaccines or passive immunization with systemic monoclonal anti-Abeta antibodies reduces amyloid deposition and improves cognition in APP transgenic mice. |
| 63 | 12736345 | The results are discussed in the context of other studies identifying coincident microglial activation and amyloid removal in APP transgenic animals. |
| 64 | 12736345 | Active immunization against the beta-amyloid peptide (Alphabeta) with vaccines or passive immunization with systemic monoclonal anti-Abeta antibodies reduces amyloid deposition and improves cognition in APP transgenic mice. |
| 65 | 12736345 | The results are discussed in the context of other studies identifying coincident microglial activation and amyloid removal in APP transgenic animals. |
| 66 | 12751917 | The evidence indicates that abnormal processing and extracellular deposition of the longer form of the beta-amyloid (Abeta) peptide (Abeta(1-42), a proteolytic derivative of the amyloid precursor protein [APP]) is implicated in the pathogenesis of Alzheimer's disease. |
| 67 | 12751917 | It has been demonstrated, using a single transgenic mouse model system that overexpresses the human mutated APP gene, that an immunisation against Abeta(1-42) causes a marked reduction in the amyloid burden in the brain. |
| 68 | 12751917 | Other studies using different approaches - such as secretase, cholesterol and Abeta metalloprotein inhibitors or NSAIDs - but all targeting the abnormal metabolism of Abeta have confirmed in each case that a significant reduction of amyloid plaque burden can be achieved in transgenic mouse models of Alzheimer's disease. |
| 69 | 12751917 | Although the first clinical trial of active immunisation with a pre-aggregated synthetic Abeta(42) preparation (AN-1792 vaccine) met with some setbacks and was discontinued after several patients experienced meningoencephalitis, the follow-up analysis of the effect of immunisation against Abeta in humans revealed a powerful effect of vaccination in the clearance of amyloid plaques from the cerebral cortex. |
| 70 | 12751917 | The evidence indicates that abnormal processing and extracellular deposition of the longer form of the beta-amyloid (Abeta) peptide (Abeta(1-42), a proteolytic derivative of the amyloid precursor protein [APP]) is implicated in the pathogenesis of Alzheimer's disease. |
| 71 | 12751917 | It has been demonstrated, using a single transgenic mouse model system that overexpresses the human mutated APP gene, that an immunisation against Abeta(1-42) causes a marked reduction in the amyloid burden in the brain. |
| 72 | 12751917 | Other studies using different approaches - such as secretase, cholesterol and Abeta metalloprotein inhibitors or NSAIDs - but all targeting the abnormal metabolism of Abeta have confirmed in each case that a significant reduction of amyloid plaque burden can be achieved in transgenic mouse models of Alzheimer's disease. |
| 73 | 12751917 | Although the first clinical trial of active immunisation with a pre-aggregated synthetic Abeta(42) preparation (AN-1792 vaccine) met with some setbacks and was discontinued after several patients experienced meningoencephalitis, the follow-up analysis of the effect of immunisation against Abeta in humans revealed a powerful effect of vaccination in the clearance of amyloid plaques from the cerebral cortex. |
| 74 | 12751917 | The evidence indicates that abnormal processing and extracellular deposition of the longer form of the beta-amyloid (Abeta) peptide (Abeta(1-42), a proteolytic derivative of the amyloid precursor protein [APP]) is implicated in the pathogenesis of Alzheimer's disease. |
| 75 | 12751917 | It has been demonstrated, using a single transgenic mouse model system that overexpresses the human mutated APP gene, that an immunisation against Abeta(1-42) causes a marked reduction in the amyloid burden in the brain. |
| 76 | 12751917 | Other studies using different approaches - such as secretase, cholesterol and Abeta metalloprotein inhibitors or NSAIDs - but all targeting the abnormal metabolism of Abeta have confirmed in each case that a significant reduction of amyloid plaque burden can be achieved in transgenic mouse models of Alzheimer's disease. |
| 77 | 12751917 | Although the first clinical trial of active immunisation with a pre-aggregated synthetic Abeta(42) preparation (AN-1792 vaccine) met with some setbacks and was discontinued after several patients experienced meningoencephalitis, the follow-up analysis of the effect of immunisation against Abeta in humans revealed a powerful effect of vaccination in the clearance of amyloid plaques from the cerebral cortex. |
| 78 | 12751917 | The evidence indicates that abnormal processing and extracellular deposition of the longer form of the beta-amyloid (Abeta) peptide (Abeta(1-42), a proteolytic derivative of the amyloid precursor protein [APP]) is implicated in the pathogenesis of Alzheimer's disease. |
| 79 | 12751917 | It has been demonstrated, using a single transgenic mouse model system that overexpresses the human mutated APP gene, that an immunisation against Abeta(1-42) causes a marked reduction in the amyloid burden in the brain. |
| 80 | 12751917 | Other studies using different approaches - such as secretase, cholesterol and Abeta metalloprotein inhibitors or NSAIDs - but all targeting the abnormal metabolism of Abeta have confirmed in each case that a significant reduction of amyloid plaque burden can be achieved in transgenic mouse models of Alzheimer's disease. |
| 81 | 12751917 | Although the first clinical trial of active immunisation with a pre-aggregated synthetic Abeta(42) preparation (AN-1792 vaccine) met with some setbacks and was discontinued after several patients experienced meningoencephalitis, the follow-up analysis of the effect of immunisation against Abeta in humans revealed a powerful effect of vaccination in the clearance of amyloid plaques from the cerebral cortex. |
| 82 | 12763682 | Long pentraxins consist of a C-terminal pentraxin domain, which has sequence similarity to C-reactive protein (CRP) and serum amyloid P (SAP) component (the classic short pentraxins), and of an unrelated N-terminal portion. |
| 83 | 12763682 | PTX3 is made by diverse cell types, most prominently endothelial cells, macrophages and dendritic cells, in response to primary inflammatory signals (e.g. interleukin-1 (IL-1), tumour necrosis factor (TNF), lipopolysaccharide (LPS)). |
| 84 | 12787077 | Vaccination against human beta-amyloid peptide (A beta) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. |
| 85 | 12787077 | A beta 40/42 were previously quantified in tissues from our well-established brain bank, including non-demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. |
| 86 | 12787077 | Vaccination against human beta-amyloid peptide (A beta) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. |
| 87 | 12787077 | A beta 40/42 were previously quantified in tissues from our well-established brain bank, including non-demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. |
| 88 | 12897198 | Alzheimer disease (AD) is characterized by the progressive accumulation of amyloid beta protein (Abeta) in areas of the brain serving cognitive functions such as memory and language. |
| 89 | 12897209 | Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. |
| 90 | 12897209 | Alzheimer disease (AD) is characterized by the progressive deposition of the 42-residue amyloid beta protein (Abeta) in brain regions serving memory and cognition. |
| 91 | 12897209 | Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. |
| 92 | 12897209 | Alzheimer disease (AD) is characterized by the progressive deposition of the 42-residue amyloid beta protein (Abeta) in brain regions serving memory and cognition. |
| 93 | 14501019 | M1 muscarinic receptors (M1 mAChRs) play a role in an apparent linkage of three major hallmarks of Alzheimer's disease (AD): beta-amyloid (Abeta) peptide; tau hyperphosphorylation and paired helical filaments (PHFs); and loss of cholinergic function conducive to cognitive impairments. |
| 94 | 14501019 | Activation of M1 mAChRs with these agonists leads, inter alia, to enhanced secretion of amyloid precursor protein (alpha-APP), (via alpha-secretase activation), to decreased Abeta (via gamma-secretase inhibition), and to inhibition of Abeta- and/or oxidative stress-induced cell death. |
| 95 | 14501019 | Studies from other labs showed that AF102B and talsaclidine (another M1 agonist) decreased cerbrospinal fluid (CSF) Abeta in AD patients following chronic treatment, being the first reported drugs with such a profile. |
| 96 | 14501019 | Remarkably, although M1 agonists can decrease CSF Abeta in AD patients, an increased AD-type pathology in Parkinson's disease was recently been associated with chronic antimuscarinic treatment. |
| 97 | 14501019 | This may place such drugs in the first line of modern AD therapies (e.g., beta- or gamma-secretase inhibitors, vaccines against Abeta, statins, and inhibitors of tau hyperphosphorylation). |
| 98 | 14514149 | Correlation between the severity of infectious diseases in children and the ratio of serum amyloid A protein and C-reactive protein. |
| 99 | 14514149 | The aim of this study was to assess whether measurements of serum amyloid A protein (SAA) could provide additional information on the severity of acute infection beyond that obtained from C-reactive protein (CRP) assays. |
| 100 | 14514149 | The SAA and CRP concentrations were analysed from the sera of 334 children hospitalized for suspected pneumonia, meningitis or sepsis. |
| 101 | 14514149 | SAA significantly correlated with CRP (r = 0.682, p < 0.001) and did not alone provide any further clinically useful information. |
| 102 | 14514149 | By contrast, the median ratio (and interquartile range) of SAA to CRP varied significantly between clinical conditions of different severity and was significantly lower in the patients who died [1.9 (0.0-8.9)] than in those who survived [6.8 (3.2-13.6)] (p = 0.001). |
| 103 | 14514149 | Correlation between the severity of infectious diseases in children and the ratio of serum amyloid A protein and C-reactive protein. |
| 104 | 14514149 | The aim of this study was to assess whether measurements of serum amyloid A protein (SAA) could provide additional information on the severity of acute infection beyond that obtained from C-reactive protein (CRP) assays. |
| 105 | 14514149 | The SAA and CRP concentrations were analysed from the sera of 334 children hospitalized for suspected pneumonia, meningitis or sepsis. |
| 106 | 14514149 | SAA significantly correlated with CRP (r = 0.682, p < 0.001) and did not alone provide any further clinically useful information. |
| 107 | 14514149 | By contrast, the median ratio (and interquartile range) of SAA to CRP varied significantly between clinical conditions of different severity and was significantly lower in the patients who died [1.9 (0.0-8.9)] than in those who survived [6.8 (3.2-13.6)] (p = 0.001). |
| 108 | 14635031 | Active immunization with fibrillar beta-amyloid peptide (Abeta(42)) as well as passive transfer of anti-Abeta antibodies significantly reduces Abeta plaque deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid precursor protein (APP)-transgenic mice. |
| 109 | 14635031 | We constructed a DNA minigene with Abeta fused to mouse interleukin-4 (pAbeta(42)-IL-4) as a molecular adjuvant to generate anti-Abeta antibodies and enhance the Th2-type of immune responses. |
| 110 | 14678754 | A single administration of the AAV-CB-Abeta42 vaccine induced a prolonged, strong production of Abeta-specific serum IgG in transgenic mice that overexpressed the London mutant of amyloid precursor protein (APP/V717I), and resulted in improved ability of memory and cognition, decreased Abeta deposition in the brain, and a resultant decrease in plaque-associated astrocytosis. |
| 111 | 14743443 | Alzheimer's disease (AD) is characterized in part by the deposition of amyloid beta protein (Abeta) in compact fibrillar plaques. |
| 112 | 14751766 | The mechanisms by which anti-Abeta antibodies clear amyloid plaques in Abeta depositing transgenic mice are unclear. |
| 113 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 114 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 115 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 116 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 117 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 118 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 119 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 120 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 121 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 122 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 123 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 124 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 125 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 126 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 127 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 128 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 129 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 130 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 131 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 132 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 133 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 134 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 135 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 136 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 137 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 138 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 139 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 140 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 141 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 142 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 143 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 144 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 145 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 146 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 147 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 148 | 14997933 | Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. |
| 149 | 14997933 | Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. |
| 150 | 14997933 | The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. |
| 151 | 14997933 | Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. |
| 152 | 14997933 | Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. |
| 153 | 14997933 | These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. |
| 154 | 14997933 | Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. |
| 155 | 15095177 | In-vitro studies demonstrated that monoclonal antibodies could modulate the conformation of Abeta peptides with subsequent inhibition of amyloid fibrils formation and aggregation. |
| 156 | 15170082 | The most plausible mechanism for the treatment of AD is the reduction of the amyloid beta-peptide (Abeta) plaques, one of the pathological markers of AD, in the brain. |
| 157 | 15170082 | For this purpose, the inhibitors of beta-secretase and gamma-secretase, which cleave amyloid precursor protein (APP) to release Abeta, has been developed to interfere with APP processing. |
| 158 | 15170082 | The most plausible mechanism for the treatment of AD is the reduction of the amyloid beta-peptide (Abeta) plaques, one of the pathological markers of AD, in the brain. |
| 159 | 15170082 | For this purpose, the inhibitors of beta-secretase and gamma-secretase, which cleave amyloid precursor protein (APP) to release Abeta, has been developed to interfere with APP processing. |
| 160 | 15171563 | The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides-Abeta40 and Abeta42. |
| 161 | 15171563 | The Abeta peptides are derived from the amyloid precursor protein (APP) which is considered very important for the AD pathogenesis. |
| 162 | 15171563 | In recent years, studies have focused on understanding the generation of Abeta peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and progression of both familial and sporadic AD (FAD and SAD). |
| 163 | 15171563 | This review covers the trafficking and processing of APP, the amyloid cascade hypothesis in AD pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset and late-onset AD. |
| 164 | 15171563 | The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides-Abeta40 and Abeta42. |
| 165 | 15171563 | The Abeta peptides are derived from the amyloid precursor protein (APP) which is considered very important for the AD pathogenesis. |
| 166 | 15171563 | In recent years, studies have focused on understanding the generation of Abeta peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and progression of both familial and sporadic AD (FAD and SAD). |
| 167 | 15171563 | This review covers the trafficking and processing of APP, the amyloid cascade hypothesis in AD pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset and late-onset AD. |
| 168 | 15171563 | The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides-Abeta40 and Abeta42. |
| 169 | 15171563 | The Abeta peptides are derived from the amyloid precursor protein (APP) which is considered very important for the AD pathogenesis. |
| 170 | 15171563 | In recent years, studies have focused on understanding the generation of Abeta peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and progression of both familial and sporadic AD (FAD and SAD). |
| 171 | 15171563 | This review covers the trafficking and processing of APP, the amyloid cascade hypothesis in AD pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset and late-onset AD. |
| 172 | 15195462 | Alzheimer disease (AD) is the most prevalent form of dementia worldwide and is characterized by the progressive accumulation of the 42-residue amyloid beta protein (A beta) in brain regions serving memory and cognition. |
| 173 | 15215183 | By Day 42, immunized animals generated plasma Abeta antibodies that labeled Abeta plaques in human, AD transgenic mouse and vervet brains; bound Abeta1-7; and recognized monomeric and oligomeric Abeta but not full-length amyloid precursor protein nor its C-terminal fragments. |
| 174 | 15241501 | The neuropathology of Alzheimer's disease(AD) is characterized by the accumulation of amyloid peptide Abeta in the brain derived from proteolytic cleavage of the amyloid precursor protein (APP). |
| 175 | 15241501 | Both immune sera and monoclonal antibodies solubilized preformed aggregates of Abeta42 in vitro and recognized amyloid plaques in brain sections of mice transgenic for human APP. |
| 176 | 15241501 | The neuropathology of Alzheimer's disease(AD) is characterized by the accumulation of amyloid peptide Abeta in the brain derived from proteolytic cleavage of the amyloid precursor protein (APP). |
| 177 | 15241501 | Both immune sera and monoclonal antibodies solubilized preformed aggregates of Abeta42 in vitro and recognized amyloid plaques in brain sections of mice transgenic for human APP. |
| 178 | 15270200 | At the biochemical level, copper, zinc and iron were shown to accelerate the aggregation of the Abeta peptide and enhance metal catalyzed oxidative stress associated with amyloid plaque formation. |
| 179 | 15270200 | Based on the presence of both an Interleukin-1 (IL-1) responsive acute box domain and an IRE in the APP 5'UTR, we predict that our APP 5'UTR directed drug screens will identify both novel metal chelators and novel NSAIDS. |
| 180 | 15270200 | These lead drugs are readily testable to measure APP holoprotein expression in a cell based secondary assay, and by use of an APP transgenic mouse model to test potential beneficial effects of lead drug treatments on amyloid burden. |
| 181 | 15270200 | At the biochemical level, copper, zinc and iron were shown to accelerate the aggregation of the Abeta peptide and enhance metal catalyzed oxidative stress associated with amyloid plaque formation. |
| 182 | 15270200 | Based on the presence of both an Interleukin-1 (IL-1) responsive acute box domain and an IRE in the APP 5'UTR, we predict that our APP 5'UTR directed drug screens will identify both novel metal chelators and novel NSAIDS. |
| 183 | 15270200 | These lead drugs are readily testable to measure APP holoprotein expression in a cell based secondary assay, and by use of an APP transgenic mouse model to test potential beneficial effects of lead drug treatments on amyloid burden. |
| 184 | 15294135 | Clearing tau pathology with Abeta immunotherapy--reversible and irreversible stages revealed. |
| 185 | 15294135 | The report by Oddo and colleagues in this issue of Neuron demonstrates for the first time that clearance of amyloid also results in the removal of early-stage tau pathology in mice that develop both amyloid plaques and neurofibrillary tangles (NFT), the two hallmark lesions of Alzheimer's disease (AD). |
| 186 | 15342006 | Clinical trials involving Abeta immunotherapy for AD are in progress and are providing a wealth of information around the amyloid hypothesis of AD. |
| 187 | 15530403 | For the fundamental treatment of AD, an amyloid beta protein (Abeta) vaccine is considered to be the most potent candidate. |
| 188 | 15651289 | Since active and passive immunization of amyloid precursor protein (APP) gene- transgenic mice showed significant reduction of beta amyloid deposits in the brain and the immunized mice showed improvement in cognitive functions, clinical trials were performed in US and Europe. |
| 189 | 15653168 | Given the participation of amyloid beta (Abeta) in Alzheimer's disease (AD) pathogenesis the derivation of experimental therapeutics to prevent Abeta fibrillogenesis and/or enhance removal of parenchymal amyloid deposits represent viable disease-modifying approaches. |
| 190 | 15661919 | Immunization of amyloid precursor protein transgenic mice with fibrillar beta-amyloid (Abeta) prevents Alzheimer's disease (AD)-like neuropathology. |
| 191 | 15694248 | We have previously demonstrated that intracerebroventricular (ICV) injection of anti-Abeta (IgG1, kappa against the 1-28 region of Abeta) reduced cerebral amyloid plaques by 50% after 1 month without producing hemorrhage or activating IL-1beta responses in Tg2576 brain [N.B. |
| 192 | 15731045 | Concentrations of serum amyloid A (SAA) increased significantly 3 h after both the primary (P <0.05) and booster (P <0.001) i.m. vaccinations, but not in i.n. vaccinated calves. |
| 193 | 15811643 | Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF. |
| 194 | 15811643 | Lines of experimental evidence indicate that induction of humoral immune responses in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic amyloid beta-protein (Abeta) is effective in prevention and clearance of deposits of Abeta aggregates in the brain of the mice. |
| 195 | 15811643 | By co-immunization with an adenovirus vector encoding granulocyte-macrophage colony stimulating factor (GM-CSF), the adenovirus vector encoding Abeta effectively elicited an immune response against Abeta. |
| 196 | 15811643 | Induction of a Th2 immune response by co-administration of recombinant adenovirus vectors encoding amyloid beta-protein and GM-CSF. |
| 197 | 15811643 | Lines of experimental evidence indicate that induction of humoral immune responses in transgenic mouse models of Alzheimer disease (AD) by repeated injection of synthetic amyloid beta-protein (Abeta) is effective in prevention and clearance of deposits of Abeta aggregates in the brain of the mice. |
| 198 | 15811643 | By co-immunization with an adenovirus vector encoding granulocyte-macrophage colony stimulating factor (GM-CSF), the adenovirus vector encoding Abeta effectively elicited an immune response against Abeta. |
| 199 | 15971572 | Abeta specific antibodies are believed to cross blood-brain barrier by minimal destroy of vascular wall where amyloid depositions exist. |
| 200 | 15976761 | Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. |
| 201 | 15976761 | The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). |
| 202 | 15976761 | No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. |
| 203 | 15976761 | Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. |
| 204 | 15976761 | The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). |
| 205 | 15976761 | No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. |
| 206 | 16126169 | Induction of an immune response to amyloid beta-protein (Abeta) is effective in treating animal models of Alzheimer's disease. |
| 207 | 16126169 | Here, we show that an adenovirus vector encoding 11 tandem repeats of Abeta1-6 can induce an immune response against amyloid beta-protein. |
| 208 | 16126169 | Much higher titers against amyloid beta-protein were observed when an adenovirus vector encoding GM-CSF was co-administered. |
| 209 | 16126169 | Induction of an immune response to amyloid beta-protein (Abeta) is effective in treating animal models of Alzheimer's disease. |
| 210 | 16126169 | Here, we show that an adenovirus vector encoding 11 tandem repeats of Abeta1-6 can induce an immune response against amyloid beta-protein. |
| 211 | 16126169 | Much higher titers against amyloid beta-protein were observed when an adenovirus vector encoding GM-CSF was co-administered. |
| 212 | 16126169 | Induction of an immune response to amyloid beta-protein (Abeta) is effective in treating animal models of Alzheimer's disease. |
| 213 | 16126169 | Here, we show that an adenovirus vector encoding 11 tandem repeats of Abeta1-6 can induce an immune response against amyloid beta-protein. |
| 214 | 16126169 | Much higher titers against amyloid beta-protein were observed when an adenovirus vector encoding GM-CSF was co-administered. |
| 215 | 16157426 | In this study, we examine both humoral and cellular immune responses elicited by immunization with peptide or DNA encoding wild-type and the Flemish and Dutch mutations of ABeta42 (i.e. the beta amyloid peptide spanning amino acids 1-42) in mice of different immune haplotypes as well as HLA Class II transgenic mice. |
| 216 | 16187407 | Local serum amyloid A (SAA) formation may be involved in deposition of AA-amyloid induced by conformational change of SAA resulting in amyloid formation, having tremendous food safety implications. |
| 217 | 16240877 | The pivotal role of the proteolytic processing of the amyloid precursor protein (APP) in neuronal death suggests pharmacological inhibition of the secretases; amyloid antiaggregant therapies are possible, vaccination against AB wil need new immunisation protocols, Anti-inflammatory drugs and antioxydant agents as calcium channel blockers could help against the neurotoxic cascade of Abeta, some cholesterol-lowering drugs could enhance its clearance. |
| 218 | 16289870 | According to the amyloid cascade hypothesis, deposition of Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased Abeta levels. |
| 219 | 16293586 | Vaccine-based approaches have been developed to target and eliminate amyloid beta (Abeta), a key peptide implicated in AD pathogenesis. |
| 220 | 16310782 | Beta amyloid (Abeta) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of Abeta is considered a primary therapeutic target. |
| 221 | 16322661 | The major component of AD plaques is beta-amyloid, a 40 to 42 amino acid polypeptide derived from the amyloid precursor protein (APP) by proteolytic degradation involving the specific proteases, beta-and gamma-secretase acting at the N- and C- terminal cleavage site, respectively. |
| 222 | 16489369 | The extracellular amyloid plaque deposits are composed of a proteinacious core of insoluble aggregated amyloid-beta (Abeta) peptide and have led to the foundation of the amyloid hypothesis. |
| 223 | 16672644 | Immunization of human amyloid precursor protein, familial AD (hAPP(FAD)) mice with R-2xAbeta1-15 or 2xAbeta1-15 resulted in high anti-Abeta titers of noninflammatory T-helper 2 isotypes (IgG1 and IgG2b), a lack of splenocyte proliferation against full-length Abeta, significantly reduced Abeta plaque load, and lower cerebral Abeta levels. |
| 224 | 16672644 | In addition, 2xAbeta1-15-immunized hAPP(FAD) animals showed improved acquisition of memory compared with vehicle controls in a reference-memory Morris water-maze behavior test that approximately correlated with anti-Abeta titers. |
| 225 | 16690718 | Interestingly, a cholinesterase inhibitor currently in clinical trials, phenserine, has been shown to inhibit production of both amyloid precursor protein (APP) and A beta. |
| 226 | 16690718 | The focus of this study was to screen 144 analogs of phenserine to identify additional small molecules that inhibit APP protein synthesis, and thereby A beta production, without possessing potent acetylcholinesterase (AChE) inhibitory activity. |
| 227 | 16769900 | It was recently demonstrated that amyloid beta (Abeta) peptide vaccination was effective in reducing the Abeta burden in Alzheimer model mice. |
| 228 | 16908970 | In this study, we produced an Hsp70-supported vaccine to induce the generation of antibodies against amyloid-beta (Abeta) peptides, the major constituent of beta-amyloid plaques in Alzheimer's disease. |
| 229 | 16908970 | Prophylactic short-term immunization of transgenic mice (APP tg2576) before the onset of plaques, however, did not prevent amyloid plaque deposition. |
| 230 | 16936277 | Experiments with amyloid-beta (Abeta)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. |
| 231 | 16936277 | Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Abeta peptides. |
| 232 | 16936277 | Experiments with amyloid-beta (Abeta)-42-immunized transgenic mouse models of Alzheimer's disease have revealed amyloid plaque disruption and apparent cognitive function recovery. |
| 233 | 16936277 | Our experiments suggest that although immunization disrupted amyloid deposits, vascular capture prevented large-scale egress of Abeta peptides. |
| 234 | 16972884 | Interestingly, LAMP-1 immunoreactivity has little correlation with phosphorylated tau deposition and neurofibrillary tangles (NFTs), as neurones with NFTs were rarely LAMP-1 immunoreactive. |
| 235 | 16972884 | Finally, LAMP-1 occurred in microglia and multinucleated giant cells in one AD case in whom amyloid burden was cleared following betaA-peptide immunization. |
| 236 | 16972888 | Resolution process of cerebroparenchymal amyloid beta-protein (Abeta) deposition has become of increasing interest in the light of recent advance in the Abeta-vaccination therapy for Alzheimer's disease (AD). |
| 237 | 16972888 | To clarify the natural removal processes of Abeta burden in the brain with AD, we devised a triple-step staining method: Bodian for dystrophic neurites, anti-glial fibrillary acidic protein for astrocytes, and anti-Abeta. |
| 238 | 17076654 | An improved understanding of the pathogeneses of AD has now led to the identification of numerous therapeutic targets designed to alter amyloid beta protein (Abeta) or tau accumulation. |
| 239 | 17076654 | Therapies that alter Abeta and tau through these various targets are likely to have significant disease modifying effects. |
| 240 | 17076654 | Many of these targets have been validated in proof of concept studies in preclinical animal models, and some potentially disease modifying therapies targeting Abeta or tau are being tested in the clinic. |
| 241 | 17079673 | Increased T cell recruitment to the CNS after amyloid beta 1-42 immunization in Alzheimer's mice overproducing transforming growth factor-beta 1. |
| 242 | 17079673 | Immunotherapy targeting the amyloid beta (Abeta) peptide is a novel therapy under investigation for the treatment of Alzheimer's disease (AD). |
| 243 | 17079673 | Furthermore, TGF-beta1 overexpression in a mouse model for AD [amyloid precursor protein (APP) mice] leads to development of additional T cell infiltrates when mice were immunized at a young but not old age with AN1792. |
| 244 | 17079673 | Notably, only mice overproducing both Abeta (APP mice) and TGF-beta1 experienced a rise in T lymphocyte number after immunization. |
| 245 | 17079673 | These results demonstrate that TGF-beta1 overproduction in the brain can promote T cell infiltration, in particular after Abeta(1-42) immunization. |
| 246 | 17079673 | Likewise, levels of TGF-beta1 or other immune factors in brains of AD patients may influence the response to Abeta(1-42) immunization. |
| 247 | 17079673 | Increased T cell recruitment to the CNS after amyloid beta 1-42 immunization in Alzheimer's mice overproducing transforming growth factor-beta 1. |
| 248 | 17079673 | Immunotherapy targeting the amyloid beta (Abeta) peptide is a novel therapy under investigation for the treatment of Alzheimer's disease (AD). |
| 249 | 17079673 | Furthermore, TGF-beta1 overexpression in a mouse model for AD [amyloid precursor protein (APP) mice] leads to development of additional T cell infiltrates when mice were immunized at a young but not old age with AN1792. |
| 250 | 17079673 | Notably, only mice overproducing both Abeta (APP mice) and TGF-beta1 experienced a rise in T lymphocyte number after immunization. |
| 251 | 17079673 | These results demonstrate that TGF-beta1 overproduction in the brain can promote T cell infiltration, in particular after Abeta(1-42) immunization. |
| 252 | 17079673 | Likewise, levels of TGF-beta1 or other immune factors in brains of AD patients may influence the response to Abeta(1-42) immunization. |
| 253 | 17079673 | Increased T cell recruitment to the CNS after amyloid beta 1-42 immunization in Alzheimer's mice overproducing transforming growth factor-beta 1. |
| 254 | 17079673 | Immunotherapy targeting the amyloid beta (Abeta) peptide is a novel therapy under investigation for the treatment of Alzheimer's disease (AD). |
| 255 | 17079673 | Furthermore, TGF-beta1 overexpression in a mouse model for AD [amyloid precursor protein (APP) mice] leads to development of additional T cell infiltrates when mice were immunized at a young but not old age with AN1792. |
| 256 | 17079673 | Notably, only mice overproducing both Abeta (APP mice) and TGF-beta1 experienced a rise in T lymphocyte number after immunization. |
| 257 | 17079673 | These results demonstrate that TGF-beta1 overproduction in the brain can promote T cell infiltration, in particular after Abeta(1-42) immunization. |
| 258 | 17079673 | Likewise, levels of TGF-beta1 or other immune factors in brains of AD patients may influence the response to Abeta(1-42) immunization. |
| 259 | 17086100 | There was resolution of tau-containing dystrophic neurites, although other features of tau pathology (tangles and neuropil threads) remained and cerebral amyloid angiopathy persisted. |
| 260 | 17086100 | However, if it is to be used for treatment of established Alzheimer disease, then the residual tau pathology and cerebral amyloid angiopathy require further study. |
| 261 | 17086100 | There was resolution of tau-containing dystrophic neurites, although other features of tau pathology (tangles and neuropil threads) remained and cerebral amyloid angiopathy persisted. |
| 262 | 17086100 | However, if it is to be used for treatment of established Alzheimer disease, then the residual tau pathology and cerebral amyloid angiopathy require further study. |
| 263 | 17105428 | Despite these setbacks, clinical trials have demonstrated the utility of amyloid-beta (Abeta) vaccination in reducing amyloid pathology and potentially reducing cognitive decline. |
| 264 | 17105428 | If so, Abeta vaccination could supplant current symptomatic treatment and represent one of the first therapeutic options for AD based on the amyloid cascade hypothesis. |
| 265 | 17105428 | Despite these setbacks, clinical trials have demonstrated the utility of amyloid-beta (Abeta) vaccination in reducing amyloid pathology and potentially reducing cognitive decline. |
| 266 | 17105428 | If so, Abeta vaccination could supplant current symptomatic treatment and represent one of the first therapeutic options for AD based on the amyloid cascade hypothesis. |
| 267 | 17134029 | [Molecular pathology and therapeutics in Alzheimer's disease: amyloid beta-protein as a therapeutic target]. |
| 268 | 17137722 | Vaccination with Abeta(1-42) and treatment with NCX-2216, a novel nitric oxide releasing flurbiprofen derivative, have each been shown separately to reduce amyloid deposition in transgenic mice and have been suggested as potential therapies for Alzheimer's disease. |
| 269 | 17137722 | In the current study we treated doubly transgenic amyloid precursor protein and presenilin-1 (APP+PS1) mice with Abeta(1-42) vaccination, NCX-2216 or both drugs simultaneously for 9 months. |
| 270 | 17137722 | We also found that active Abeta vaccination resulted in significantly increased cerebral amyloid angiopathy and associated microhemorrhages, while NCX-2216 did not, in spite of similar reductions in parenchymal amyloid. |
| 271 | 17137722 | Vaccination with Abeta(1-42) and treatment with NCX-2216, a novel nitric oxide releasing flurbiprofen derivative, have each been shown separately to reduce amyloid deposition in transgenic mice and have been suggested as potential therapies for Alzheimer's disease. |
| 272 | 17137722 | In the current study we treated doubly transgenic amyloid precursor protein and presenilin-1 (APP+PS1) mice with Abeta(1-42) vaccination, NCX-2216 or both drugs simultaneously for 9 months. |
| 273 | 17137722 | We also found that active Abeta vaccination resulted in significantly increased cerebral amyloid angiopathy and associated microhemorrhages, while NCX-2216 did not, in spite of similar reductions in parenchymal amyloid. |
| 274 | 17137722 | Vaccination with Abeta(1-42) and treatment with NCX-2216, a novel nitric oxide releasing flurbiprofen derivative, have each been shown separately to reduce amyloid deposition in transgenic mice and have been suggested as potential therapies for Alzheimer's disease. |
| 275 | 17137722 | In the current study we treated doubly transgenic amyloid precursor protein and presenilin-1 (APP+PS1) mice with Abeta(1-42) vaccination, NCX-2216 or both drugs simultaneously for 9 months. |
| 276 | 17137722 | We also found that active Abeta vaccination resulted in significantly increased cerebral amyloid angiopathy and associated microhemorrhages, while NCX-2216 did not, in spite of similar reductions in parenchymal amyloid. |
| 277 | 17163576 | Genes identified in MLN and tonsils corresponded to serum amyloid A, arginase I, osteopontin, lysozyme, annexin I, and heat shock proteins, respectively. |
| 278 | 17163576 | Five proteins, including stress/inflammatory proteins annexin V, serum albumin, and apolipoprotein A1 were found at lower levels in MLN of TB+ boars. |
| 279 | 17163576 | Manganese superoxide dismutase was found up-regulated in MLN of TB+ boars. |
| 280 | 17219449 | Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Abeta1-6 upregulates IL-10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9 mouse model of Alzheimer's disease. |
| 281 | 17335831 | We compared changes in plasma C-reactive protein (CRP) and serum amyloid A (SAA) concentrations 48 h after a standardized inflammatory stimulus (adjuvanted influenza vaccination) in patients with quiescent CHD that had been manifested at onset as inducible myocardial ischemia (Group 1, n=26) or as acute coronary syndromes (ACS) (Group 2, n=34). |
| 282 | 17335831 | Changes in CRP and SAA, both absolute and percentage, were significantly correlated in Group 2 (r=0.60 and 0.66, both p<0.001). |
| 283 | 17353506 | Toxic human islet amyloid polypeptide (h-IAPP) oligomers are intracellular, and vaccination to induce anti-toxic oligomer antibodies does not prevent h-IAPP-induced beta-cell apoptosis in h-IAPP transgenic mice. |
| 284 | 17517595 | Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. |
| 285 | 17517595 | Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated amyloid 1-15 peptide (palmAbeta(1-15)), or with amyloid 1-16 peptide (PEG-Abeta(1-16)) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. |
| 286 | 17517595 | Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. |
| 287 | 17517595 | Inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetra-palmitoylated amyloid 1-15 peptide (palmAbeta(1-15)), or with amyloid 1-16 peptide (PEG-Abeta(1-16)) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. |
| 288 | 17686533 | Accumulation of aggregated amyloid beta-protein (Abeta) in the brain is thought to be the initiating event leading to neurodegeneration and dementia in Alzheimer's disease (AD). |
| 289 | 17867462 | Serum amyloid A (SAA) is of interest as the circulating precursor of amyloid A protein, the fibrillar component of AA (secondary) amyloid deposits, and also as an extremely sensitive and rapid major acute phase protein. |
| 290 | 17869376 | Promising therapeutic results have been obtained utilizing amyloid precursor protein (APP) transgenic (tg) models of AD to develop therapies including use of inhibitors of the APP-processing enzymes beta- and gamma-secretase as well as vaccine therapies. |
| 291 | 17962945 | In turn, the onset of the immunological eclipse was coincidental with the onset of a systemic inflammatory condition characterized by a high number of circulating and splenic polymorphonucleated neutrophils (PMN) displaying activation and Gr1(+)Mac1(+) phenotype and an increasing serum concentration of the pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 cytokines and C-reactive protein (CRP) and serum A amyloid (SAA) phase acute proteins. |
| 292 | 18003852 | Alzheimer's disease peptide epitope vaccine reduces insoluble but not soluble/oligomeric Abeta species in amyloid precursor protein transgenic mice. |
| 293 | 18003852 | Here, we describe a second generation epitope vaccine composed of two copies of Abeta(1-11) fused with the promiscuous nonself T cell epitope, PADRE (pan human leukocyte antigen DR-binding peptide) that completely eliminates the autoreactive T cell responses and induces humoral immune responses in amyloid precursor protein transgenic 2576 mice with pre-existing AD-like pathology. |
| 294 | 18003852 | Alzheimer's disease peptide epitope vaccine reduces insoluble but not soluble/oligomeric Abeta species in amyloid precursor protein transgenic mice. |
| 295 | 18003852 | Here, we describe a second generation epitope vaccine composed of two copies of Abeta(1-11) fused with the promiscuous nonself T cell epitope, PADRE (pan human leukocyte antigen DR-binding peptide) that completely eliminates the autoreactive T cell responses and induces humoral immune responses in amyloid precursor protein transgenic 2576 mice with pre-existing AD-like pathology. |
| 296 | 18055209 | CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation. |
| 297 | 18055209 | Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and memory impairment in transgenic mouse models of Alzheimer's disease (AD). |
| 298 | 18055209 | We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates Abeta-induced inflammatory responses and enhances Abeta clearance. |
| 299 | 18055209 | Further reduction of cerebral amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from brain to blood, but was rather correlated with anti-inflammatory cytokine profiles and reduced plasma soluble CD40L. |
| 300 | 18055209 | CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation. |
| 301 | 18055209 | Amyloid-beta (Abeta) immunization efficiently reduces amyloid plaque load and memory impairment in transgenic mouse models of Alzheimer's disease (AD). |
| 302 | 18055209 | We have shown that blocking the CD40-CD40 ligand (L) interaction mitigates Abeta-induced inflammatory responses and enhances Abeta clearance. |
| 303 | 18055209 | Further reduction of cerebral amyloidosis in Abeta-immunized PSAPP mice completely deficient for CD40 occurred in the absence of Abeta immunoglobulin G (IgG) antibodies or efflux of Abeta from brain to blood, but was rather correlated with anti-inflammatory cytokine profiles and reduced plasma soluble CD40L. |
| 304 | 18057195 | Novel amyloid precursor protein transgenic mice, which contain the Swedish as well as the vasculotropic Dutch and Iowa mutations (Tg-SwDI), were used to investigate the mechanisms of antibody-mediated clearance of amyloid-beta (Abeta) from the brain. |
| 305 | 18057195 | We then immunized young Tg-SwDI mice before the accumulation of Abeta and saw no evidence that anti-Abeta antibodies could diminish deposition of parenchymal or vascular amyloid deposits. |
| 306 | 18057195 | However, injection of anti-Abeta antibodies, affinity-purified from immunized Tg-SwDI mice, into the hippocampus induced a rapid clearance of diffuse Abeta deposits but not vascular amyloid deposits. |
| 307 | 18057195 | Novel amyloid precursor protein transgenic mice, which contain the Swedish as well as the vasculotropic Dutch and Iowa mutations (Tg-SwDI), were used to investigate the mechanisms of antibody-mediated clearance of amyloid-beta (Abeta) from the brain. |
| 308 | 18057195 | We then immunized young Tg-SwDI mice before the accumulation of Abeta and saw no evidence that anti-Abeta antibodies could diminish deposition of parenchymal or vascular amyloid deposits. |
| 309 | 18057195 | However, injection of anti-Abeta antibodies, affinity-purified from immunized Tg-SwDI mice, into the hippocampus induced a rapid clearance of diffuse Abeta deposits but not vascular amyloid deposits. |
| 310 | 18057195 | Novel amyloid precursor protein transgenic mice, which contain the Swedish as well as the vasculotropic Dutch and Iowa mutations (Tg-SwDI), were used to investigate the mechanisms of antibody-mediated clearance of amyloid-beta (Abeta) from the brain. |
| 311 | 18057195 | We then immunized young Tg-SwDI mice before the accumulation of Abeta and saw no evidence that anti-Abeta antibodies could diminish deposition of parenchymal or vascular amyloid deposits. |
| 312 | 18057195 | However, injection of anti-Abeta antibodies, affinity-purified from immunized Tg-SwDI mice, into the hippocampus induced a rapid clearance of diffuse Abeta deposits but not vascular amyloid deposits. |
| 313 | 18069108 | Microscopic evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration within liver, heart, and spleen, in all K6/ODC mice. |
| 314 | 18221198 | Main characteristics of Alzheimer's disease (AD) are massive cerebral accumulation of amyloid, composed of fibrillary aggregates of the Amyloid beta peptide (Abeta) and intracellular accumulation of abnormally phosphorylated tau protein associated with widespread neurodegeneration. |
| 315 | 18534566 | Antibodies to amyloid beta protein (Abeta) are present naturally or after Abeta vaccine therapy in human plasma. |
| 316 | 18814544 | Genes encoding acute phase reactants in the liver were up-regulated with serum amyloid A (SAA) as the most pronounced with a 2299-fold increase at 24 h p.i. |
| 317 | 18819689 | Alzheimer's disease is characterized by two main lesions: amyloid plaques and neurofibrillary tangles composed of aggregated A Beta peptides and hyperphosphorylated tau. |
| 318 | 18953056 | A major feature of Alzheimer's disease is the accumulation of amyloid-beta peptide (Abeta) in the brain both in the form of plaques in the cerebral cortex and in blood vessel as cerebral amyloid angiopathy (CAA). |
| 319 | 19127484 | The lack of progress in mechanistic approaches (the amyloid and tau hypotheses) to developing new AD drugs indicates that some of the basic assumptions of AD causality and the search for effective drugs are probably in need of major reassessment and redirection. |
| 320 | 19221518 | In 1999, Schenk et al. reported for the first time that amyloid beta (Abeta) deposits in AD model mice could be reduced by active vaccination with Abeta peptide. |
| 321 | 19275636 | According to the amyloid hypothesis, Abeta peptides initiate the other pathologies characteristic for AD including cognitive deficits. |
| 322 | 19305740 | However, clinical trials of anti-inflammatories have not shown effectiveness, and in recent years, the concept of immune therapy has become a treatment option as animal studies and clinical trials with Abeta vaccines have demonstrated enhanced amyloid removal through stimulation of microglial phagocytosis.This review will examine the current status of whether inhibiting inflammation is a valid therapeutic target for treating AD; what lessons have come from the clinical trials; what new pathways and classes of agents are being considered; and how this field of research can progress towards new therapeutics. |
| 323 | 19553436 | Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). |
| 324 | 19553436 | Due to limitations in available animal models, however, it has been unclear whether targeting amyloid is sufficient to reduce the other pathological hallmarks of AD-namely, accumulation of pathological, nonmutated tau and neuronal loss. |
| 325 | 19553436 | These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits. |
| 326 | 19553436 | Vaccinated APPSwDI/NOS2(-/-) mice, which have predominantly vascular amyloid pathology, showed a 30% decrease in brain A beta and a 35-45% reduction in hyperphosphorylated tau. |
| 327 | 19553436 | Nevertheless, by providing evidence that reducing amyloid pathology also reduces nonmutant tau pathology and blocks neuron loss, these data support the development of amyloid-lowering therapies for disease-modifying treatment of AD. |
| 328 | 19553436 | Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). |
| 329 | 19553436 | Due to limitations in available animal models, however, it has been unclear whether targeting amyloid is sufficient to reduce the other pathological hallmarks of AD-namely, accumulation of pathological, nonmutated tau and neuronal loss. |
| 330 | 19553436 | These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits. |
| 331 | 19553436 | Vaccinated APPSwDI/NOS2(-/-) mice, which have predominantly vascular amyloid pathology, showed a 30% decrease in brain A beta and a 35-45% reduction in hyperphosphorylated tau. |
| 332 | 19553436 | Nevertheless, by providing evidence that reducing amyloid pathology also reduces nonmutant tau pathology and blocks neuron loss, these data support the development of amyloid-lowering therapies for disease-modifying treatment of AD. |
| 333 | 19553436 | Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). |
| 334 | 19553436 | Due to limitations in available animal models, however, it has been unclear whether targeting amyloid is sufficient to reduce the other pathological hallmarks of AD-namely, accumulation of pathological, nonmutated tau and neuronal loss. |
| 335 | 19553436 | These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits. |
| 336 | 19553436 | Vaccinated APPSwDI/NOS2(-/-) mice, which have predominantly vascular amyloid pathology, showed a 30% decrease in brain A beta and a 35-45% reduction in hyperphosphorylated tau. |
| 337 | 19553436 | Nevertheless, by providing evidence that reducing amyloid pathology also reduces nonmutant tau pathology and blocks neuron loss, these data support the development of amyloid-lowering therapies for disease-modifying treatment of AD. |
| 338 | 19553436 | Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). |
| 339 | 19553436 | Due to limitations in available animal models, however, it has been unclear whether targeting amyloid is sufficient to reduce the other pathological hallmarks of AD-namely, accumulation of pathological, nonmutated tau and neuronal loss. |
| 340 | 19553436 | These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits. |
| 341 | 19553436 | Vaccinated APPSwDI/NOS2(-/-) mice, which have predominantly vascular amyloid pathology, showed a 30% decrease in brain A beta and a 35-45% reduction in hyperphosphorylated tau. |
| 342 | 19553436 | Nevertheless, by providing evidence that reducing amyloid pathology also reduces nonmutant tau pathology and blocks neuron loss, these data support the development of amyloid-lowering therapies for disease-modifying treatment of AD. |
| 343 | 19553436 | Shown to lower amyloid deposits and improve cognition in APP transgenic mouse models, immunotherapy appears to be a promising approach for the treatment of Alzheimer's disease (AD). |
| 344 | 19553436 | Due to limitations in available animal models, however, it has been unclear whether targeting amyloid is sufficient to reduce the other pathological hallmarks of AD-namely, accumulation of pathological, nonmutated tau and neuronal loss. |
| 345 | 19553436 | These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits. |
| 346 | 19553436 | Vaccinated APPSwDI/NOS2(-/-) mice, which have predominantly vascular amyloid pathology, showed a 30% decrease in brain A beta and a 35-45% reduction in hyperphosphorylated tau. |
| 347 | 19553436 | Nevertheless, by providing evidence that reducing amyloid pathology also reduces nonmutant tau pathology and blocks neuron loss, these data support the development of amyloid-lowering therapies for disease-modifying treatment of AD. |
| 348 | 19865176 | Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-beta (Abeta(42)) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Abeta immune responses in wild-type and amyloid precursor protein transgenic animals. |
| 349 | 20012091 | In the case of AD the normal soluble amyloid beta (sAbeta) peptide is converted into oligomeric/fibrillar Abeta. |
| 350 | 20012091 | The oligomeric forms of Abeta are thought to be the most toxic, while fibrillar Abeta becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. |
| 351 | 20012091 | In the case of AD the normal soluble amyloid beta (sAbeta) peptide is converted into oligomeric/fibrillar Abeta. |
| 352 | 20012091 | The oligomeric forms of Abeta are thought to be the most toxic, while fibrillar Abeta becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. |
| 353 | 20030228 | As a candidate of such antibodies, we have developed TAPIR-like antibody with much higher affinity to Abeta42 than Abeta40, and it effectively deleted senile plaque amyloid and Abeta oligomers without increasing microhemorrhages. |
| 354 | 20066498 | Virus-like peptide vaccines against Abeta N-terminal or C-terminal domains reduce amyloid deposition in APP transgenic mice without addition of adjuvant. |
| 355 | 20139660 | Based on the amyloid cascade hypothesis, various strategies targeting amyloid beta protein (Abeta) have been invented for prevention and treatment of Alzheimer disease (AD). |
| 356 | 20205640 | Abeta immunotherapy has been shown to induce a marked reduction in amyloid burden and an improvement in cognitive function in animal models. |
| 357 | 20370602 | We review attempts to treat Alzheimer disease with antibodies that bind amyloid beta peptide (Abeta) and the feasibility of developing catalytic antibodies for this purpose. |
| 358 | 20451612 | After multiple immunizations the antibody response drifted toward the elevation of antibodies that recognized conformational epitopes of assembled forms of Abeta and other types of amyloid. |
| 359 | 20471477 | In AD, the normal soluble amyloid beta (sAbeta) peptide is converted into oligomeric/fibrillar Abeta. |
| 360 | 20471477 | The oligomeric forms of Abeta are thought to be the most toxic, while fibrillar Abeta becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. |
| 361 | 20471477 | Perhaps the most exciting of the therapeutic approaches being developed is immunomodulation targeting the aggregating proteins, Abeta and tau. |
| 362 | 20471477 | In AD, the normal soluble amyloid beta (sAbeta) peptide is converted into oligomeric/fibrillar Abeta. |
| 363 | 20471477 | The oligomeric forms of Abeta are thought to be the most toxic, while fibrillar Abeta becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. |
| 364 | 20471477 | Perhaps the most exciting of the therapeutic approaches being developed is immunomodulation targeting the aggregating proteins, Abeta and tau. |
| 365 | 20493257 | Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with Abeta amyloid can have unwanted, potentially lethal, side effects. |
| 366 | 20493257 | SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Abeta(1-40)- and Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. |
| 367 | 20493257 | When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Abeta peptides or brain inflammation. |
| 368 | 20493257 | When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Abeta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. |
| 369 | 20493257 | These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. |
| 370 | 20493257 | Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with Abeta amyloid can have unwanted, potentially lethal, side effects. |
| 371 | 20493257 | SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Abeta(1-40)- and Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. |
| 372 | 20493257 | When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Abeta peptides or brain inflammation. |
| 373 | 20493257 | When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Abeta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. |
| 374 | 20493257 | These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. |
| 375 | 20493257 | Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with Abeta amyloid can have unwanted, potentially lethal, side effects. |
| 376 | 20493257 | SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Abeta(1-40)- and Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. |
| 377 | 20493257 | When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Abeta peptides or brain inflammation. |
| 378 | 20493257 | When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Abeta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. |
| 379 | 20493257 | These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. |
| 380 | 20493257 | Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with Abeta amyloid can have unwanted, potentially lethal, side effects. |
| 381 | 20493257 | SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Abeta(1-40)- and Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. |
| 382 | 20493257 | When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Abeta peptides or brain inflammation. |
| 383 | 20493257 | When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Abeta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. |
| 384 | 20493257 | These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. |
| 385 | 20493257 | Vaccination has become an important therapeutic approach to the treatment of Alzheimer's disease (AD), however, immunization with Abeta amyloid can have unwanted, potentially lethal, side effects. |
| 386 | 20493257 | SDPM1 is a 20 amino acid peptide bounded by cysteines that binds tetramer forms of Abeta(1-40)- and Abeta(1-42)-amyloids and blocks subsequent Abeta amyloid aggregation. |
| 387 | 20493257 | When done prior to the onset of amyloid plaque formation, SDPM1 vaccination of APPswePSEN1(A246E) transgenic mice reduced amyloid plaque burden and Abeta(1-40) and Abeta(1-42) levels in the brain, improved cognitive performance in Morris water maze tests, and resulted in no increased T cell responses to immunogenic or Abeta peptides or brain inflammation. |
| 388 | 20493257 | When done after plaque burden was already significant, SDPM1 immunization still significantly reduced amyloid plaque burden and Abeta(1-40/1-42) peptide levels in APPswePSEN1(A246E) brain without inducing encephalitogenic T cell responses or brain inflammation, but treatment at this stage did not improve cognitive function. |
| 389 | 20493257 | These experiments demonstrate the efficacy of a novel vaccine approach for Alzheimer's disease where immunization with an Abeta(1-40/1-42) amyloid-specific binding and blocking peptide is used to inhibit the development of neuropathology and cognitive dysfunction. |
| 390 | 20562015 | Serum from A beta 42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. |
| 391 | 20632020 | The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. |
| 392 | 20632020 | Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. |
| 393 | 20632020 | In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. |
| 394 | 20632020 | There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. |
| 395 | 20632020 | The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. |
| 396 | 20632020 | Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. |
| 397 | 20632020 | In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. |
| 398 | 20632020 | There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. |
| 399 | 20632020 | The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. |
| 400 | 20632020 | Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. |
| 401 | 20632020 | In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. |
| 402 | 20632020 | There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. |
| 403 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 404 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 405 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 406 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 407 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 408 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 409 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 410 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 411 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 412 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 413 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 414 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 415 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 416 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 417 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 418 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 419 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 420 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 421 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 422 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 423 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 424 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 425 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 426 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 427 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 428 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 429 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 430 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 431 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 432 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 433 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 434 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 435 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 436 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 437 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 438 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 439 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 440 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 441 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 442 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 443 | 20640189 | Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. |
| 444 | 20640189 | In the present study we examined, in a transgenic model of amyloid pathology, the expression of two molecules previously implicated in decreasing the severity of autoimmune responses: TREM2 (triggering receptor expressed on myeloid cells 2) and the intracellular tolerance-associated transcript, Tmem176b (transmembrane domain protein 176b). |
| 445 | 20640189 | Tmem176b expression was highest in the inner zone of amyloid plaques, whereas TREM2 expression was highest in the outer zone. |
| 446 | 20640189 | Induced expression of TREM2 occurred co-incident with detection of thioflavine-S-positive amyloid deposits. |
| 447 | 20640189 | Transfection studies revealed that expression of TREM2 correlated negatively with motility, but correlated positively with the ability of microglia to stimulate CD4(+) T-cell proliferation, TNF (tumour necrosis factor) and CCL2 (chemokine ligand 2) production, but not IFNgamma (interferon gamma) production. |
| 448 | 20640189 | TREM2 expression also showed a positive correlation with amyloid phagocytosis in unactivated cells. |
| 449 | 20640189 | However, activating cells with LPS (lipopolysaccharide), but not IFNgamma, reduced the correlation between TREM2 expression and phagocytosis. |
| 450 | 20640189 | Taken together, these data suggest that, in vivo, Tmem176b(+) cells in closest apposition to amyloid may be the least able to clear amyloid. |
| 451 | 20675870 | In the early 1980s, the NFTs were characterized, and cerebral amyloid was purified; further the amino acid sequences of the tau protein in the NFTs and of Abeta were identified. |
| 452 | 20675870 | Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons. |
| 453 | 20675870 | On the basis of these findings, the amyloid cascade hypothesis that Abeta accumulation is the primary cause of neuronal degeneration and induces accumulation of tau in the AD brain was proposed and widely accepted. |
| 454 | 20675870 | Thus, on the basis of this hypothesis, transgenic AD mice were treated with Abeta vaccine; the Abeta amyloid plaques were eliminated, and a dramatic improvement of the behavioral deficits was observed in the treated mice. |
| 455 | 20675870 | In the early 1980s, the NFTs were characterized, and cerebral amyloid was purified; further the amino acid sequences of the tau protein in the NFTs and of Abeta were identified. |
| 456 | 20675870 | Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons. |
| 457 | 20675870 | On the basis of these findings, the amyloid cascade hypothesis that Abeta accumulation is the primary cause of neuronal degeneration and induces accumulation of tau in the AD brain was proposed and widely accepted. |
| 458 | 20675870 | Thus, on the basis of this hypothesis, transgenic AD mice were treated with Abeta vaccine; the Abeta amyloid plaques were eliminated, and a dramatic improvement of the behavioral deficits was observed in the treated mice. |
| 459 | 20675870 | In the early 1980s, the NFTs were characterized, and cerebral amyloid was purified; further the amino acid sequences of the tau protein in the NFTs and of Abeta were identified. |
| 460 | 20675870 | Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons. |
| 461 | 20675870 | On the basis of these findings, the amyloid cascade hypothesis that Abeta accumulation is the primary cause of neuronal degeneration and induces accumulation of tau in the AD brain was proposed and widely accepted. |
| 462 | 20675870 | Thus, on the basis of this hypothesis, transgenic AD mice were treated with Abeta vaccine; the Abeta amyloid plaques were eliminated, and a dramatic improvement of the behavioral deficits was observed in the treated mice. |
| 463 | 21117449 | Alzheimer's disease (AD) is the most common cause of dementia in the elderly, wherein, the accumulation of amyloid beta (Abeta) peptide as cytotoxic oligomers leads to neuropathologic changes. |
| 464 | 21117449 | Transgenic mice with brain Abeta plaques immunized with aggregated Abeta have reduced amyloid burden and improved cognitive functions. |
| 465 | 21117449 | Alzheimer's disease (AD) is the most common cause of dementia in the elderly, wherein, the accumulation of amyloid beta (Abeta) peptide as cytotoxic oligomers leads to neuropathologic changes. |
| 466 | 21117449 | Transgenic mice with brain Abeta plaques immunized with aggregated Abeta have reduced amyloid burden and improved cognitive functions. |
| 467 | 21278351 | We hypothesize that serum amyloid P component (SAP), which has a species-specific, DNA-binding ability, contributes to the differences between human and mice and then limits DNA vaccine's efficacy in vivo. |
| 468 | 21278351 | Using human promonocytic cell line THP-1-derived macrophages as a cell model, we found that cells incubated with a hSAP-DNA complex showed significant defects in innate immune activations, whereas mouse SAP had similar, albeit very weak, activities. hSAP also significantly inhibited the functions of two identified DNA sentinels, high-mobility group B protein 1 and antimicrobial peptide LL37, and redirected DNA update to FcRs leading to endocytosis and endosomal degradation. |
| 469 | 21371917 | Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. |
| 470 | 21406255 | Further in-depth investigation and comprehensive analysis of alterations in the metabolism of APP, β-amyloid, and tau protein, which have a pathological effect on cell membrane, alter phosphate exchange, and impair other key metabolic functions of the cell long before the characteristic amyloid deposition takes place, is warranted. |
| 471 | 21544098 | Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine. |
| 472 | 21544098 | Using proteomics, we showed that human serum amyloid P component (hSAP) is specifically present in human DNA-protein complexes. |
| 473 | 21544098 | Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine. |
| 474 | 21544098 | Using proteomics, we showed that human serum amyloid P component (hSAP) is specifically present in human DNA-protein complexes. |
| 475 | 21697382 | The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. |
| 476 | 21697382 | CAD106 reduced brain amyloid accumulation in two APP transgenic mouse lines. |
| 477 | 21697382 | The antibodies stained amyloid deposits on tissue sections of mouse and human brain but did not label cellular structures containing APP. |
| 478 | 21697382 | The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. |
| 479 | 21697382 | CAD106 reduced brain amyloid accumulation in two APP transgenic mouse lines. |
| 480 | 21697382 | The antibodies stained amyloid deposits on tissue sections of mouse and human brain but did not label cellular structures containing APP. |
| 481 | 21697382 | The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. |
| 482 | 21697382 | CAD106 reduced brain amyloid accumulation in two APP transgenic mouse lines. |
| 483 | 21697382 | The antibodies stained amyloid deposits on tissue sections of mouse and human brain but did not label cellular structures containing APP. |
| 484 | 21717585 | Recently, treatment strategies have focused on modifying the formation, clearance, and accumulation of this potentially neurotoxic peptide. β- and γ-secretase are responsible for the cleavage of amyloid precursor protein (APP) and the generation of Aβ peptide. |
| 485 | 21972099 | The development of transgenic mice expressing mutated forms of the human amyloid precursor protein (APP) and presenilin-1 (PS1), proteins associated with familial forms of Alzheimer's disease (AD), has provided a backbone for translational studies of potential novel drug therapies. |
| 486 | 21972099 | Such mice model some aspects of AD pathology in that they develop senile plaque-like deposits of the amyloid beta-protein (Aβ) together with inflammatory pathology and some degree of neurodegeneration. |
| 487 | 21972099 | Nevertheless, reducing the pathological features of the disease continues to be the objective of pharmacological intervention and ongoing programmes continue to use transgenic mice expressing mutated APP and PS1 transgenes in attempts to overcome issues and difficulties arising from the initial clinical trials and to explore new approaches to AD treatment. |
| 488 | 21972099 | The development of transgenic mice expressing mutated forms of the human amyloid precursor protein (APP) and presenilin-1 (PS1), proteins associated with familial forms of Alzheimer's disease (AD), has provided a backbone for translational studies of potential novel drug therapies. |
| 489 | 21972099 | Such mice model some aspects of AD pathology in that they develop senile plaque-like deposits of the amyloid beta-protein (Aβ) together with inflammatory pathology and some degree of neurodegeneration. |
| 490 | 21972099 | Nevertheless, reducing the pathological features of the disease continues to be the objective of pharmacological intervention and ongoing programmes continue to use transgenic mice expressing mutated APP and PS1 transgenes in attempts to overcome issues and difficulties arising from the initial clinical trials and to explore new approaches to AD treatment. |
| 491 | 22270715 | The upregulation of gene encoding serum amyloid P component (prototypic mouse acute phase reactant) was detected in the liver and to a lesser degree in the tumor of vaccinated mice at 24 h post-PDT vaccine treatment. |
| 492 | 23024882 | Vaccine Development to Treat Alzheimer's Disease Neuropathology in APP/PS1 Transgenic Mice. |
| 493 | 23024882 | A novel vaccine addressing the major hallmarks of Alzheimer's disease (AD), senile plaque-like deposits of amyloid beta-protein (Aβ), neurofibrillary tangle-like structures, and glial proinflammatory cytokines, has been developed. |
| 494 | 23230288 | Although LVS-infected IL-6 KO mice produced much less serum amyloid A and haptoglobin (two acute-phase proteins) than WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. |
| 495 | 23389932 | Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. |
| 496 | 23486963 | The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain. |
| 497 | 23523753 | Single point mutations in the transthyretin (TTR) gene may cause a hereditary neurodegenerative disease termed familial amyloidotic polyneuropathy (FAP) due to accelerated deposition of amyloid fibrils, resulting in peripheral and autonomic nervous system dysfunction. |
| 498 | 23523753 | Our results showed that the V30A mutation impaired the thermodynamic and kinetic stabilities of the TTR protein by increasing the extent and rate of tetramer dissociation and unfolded monomer and amyloid fibril formation, even to a greater extent than the V30M mutation under several experimental conditions. |
| 499 | 23523753 | These results suggest that the V30A mutation in the TTR gene promotes the formation of unfolded monomers and amyloid fibrils, which potentially contribute to the increased neurotoxicity and the pathology associated with this FAP family. |
| 500 | 23523753 | Single point mutations in the transthyretin (TTR) gene may cause a hereditary neurodegenerative disease termed familial amyloidotic polyneuropathy (FAP) due to accelerated deposition of amyloid fibrils, resulting in peripheral and autonomic nervous system dysfunction. |
| 501 | 23523753 | Our results showed that the V30A mutation impaired the thermodynamic and kinetic stabilities of the TTR protein by increasing the extent and rate of tetramer dissociation and unfolded monomer and amyloid fibril formation, even to a greater extent than the V30M mutation under several experimental conditions. |
| 502 | 23523753 | These results suggest that the V30A mutation in the TTR gene promotes the formation of unfolded monomers and amyloid fibrils, which potentially contribute to the increased neurotoxicity and the pathology associated with this FAP family. |
| 503 | 23523753 | Single point mutations in the transthyretin (TTR) gene may cause a hereditary neurodegenerative disease termed familial amyloidotic polyneuropathy (FAP) due to accelerated deposition of amyloid fibrils, resulting in peripheral and autonomic nervous system dysfunction. |
| 504 | 23523753 | Our results showed that the V30A mutation impaired the thermodynamic and kinetic stabilities of the TTR protein by increasing the extent and rate of tetramer dissociation and unfolded monomer and amyloid fibril formation, even to a greater extent than the V30M mutation under several experimental conditions. |
| 505 | 23523753 | These results suggest that the V30A mutation in the TTR gene promotes the formation of unfolded monomers and amyloid fibrils, which potentially contribute to the increased neurotoxicity and the pathology associated with this FAP family. |
| 506 | 23684831 | The immune response was characterized by real time PCR quantifying transcripts of interleukins IL1β, IL17, IL22, interferon gamma (IFNγ), inducible NO synthase (iNOS), immunoglobulins IgM, IgA, IgY and Ig light chain, and six genes of acute phase response including avidin, serum amyloid A, extracellular fatty acid-binding protein (Ex-FABP), immune responsive gene 1, chemokine AH221 and trappin-6. |
| 507 | 23725605 | AD pathogenesis has been associated with the accumulation, aggregation, and deposition of amyloid beta (Abeta) peptides in the brain. |
| 508 | 23725605 | Hallmarks of AD are the amyloid plaques consisting of fibrillar Abeta and neurofibrillary tangles which are intracellular fibrils of hyperphosphorylated tau protein that develop later in this disease. |
| 509 | 23725605 | The amyloid cascade hypothesis postulates that Abeta deposition is an initial event in the multifactorial pathogenesis and Abeta deposition may precede AD symptoms in some patients by at least 20 years. |
| 510 | 23725605 | AD pathogenesis has been associated with the accumulation, aggregation, and deposition of amyloid beta (Abeta) peptides in the brain. |
| 511 | 23725605 | Hallmarks of AD are the amyloid plaques consisting of fibrillar Abeta and neurofibrillary tangles which are intracellular fibrils of hyperphosphorylated tau protein that develop later in this disease. |
| 512 | 23725605 | The amyloid cascade hypothesis postulates that Abeta deposition is an initial event in the multifactorial pathogenesis and Abeta deposition may precede AD symptoms in some patients by at least 20 years. |
| 513 | 23725605 | AD pathogenesis has been associated with the accumulation, aggregation, and deposition of amyloid beta (Abeta) peptides in the brain. |
| 514 | 23725605 | Hallmarks of AD are the amyloid plaques consisting of fibrillar Abeta and neurofibrillary tangles which are intracellular fibrils of hyperphosphorylated tau protein that develop later in this disease. |
| 515 | 23725605 | The amyloid cascade hypothesis postulates that Abeta deposition is an initial event in the multifactorial pathogenesis and Abeta deposition may precede AD symptoms in some patients by at least 20 years. |
| 516 | 23784011 | Higher serum amyloid A (SAA) and C-reactive protein (CRP) levels in pre-vaccination plasma were unfavorable factors for overall survival (OS). |
| 517 | 23861639 | Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date. |
| 518 | 23977276 | The unmet need of effective therapy for Alzheimer's disease, combined with problematic pharmacological approaches, led the field to explore immunotherapy, first against amyloid peptides and recently against protein Tau. |
| 519 | 23977276 | Here we adapted the liposome-based amyloid vaccine that proved safe and efficacious, and incorporated a synthetic phosphorylated peptide to mimic the important phospho-epitope of protein Tau at residues pS396/pS404. |
| 520 | 23977276 | The unmet need of effective therapy for Alzheimer's disease, combined with problematic pharmacological approaches, led the field to explore immunotherapy, first against amyloid peptides and recently against protein Tau. |
| 521 | 23977276 | Here we adapted the liposome-based amyloid vaccine that proved safe and efficacious, and incorporated a synthetic phosphorylated peptide to mimic the important phospho-epitope of protein Tau at residues pS396/pS404. |
| 522 | 24052108 | It proposes that abnormal production of beta amyloid protein (Abeta) is the cause of AD and that the neurotoxicity is due to Abeta itself or its oligomeric forms. |
| 523 | 24052108 | AD probably results from the inflammatory response induced by extracellular Abeta deposits, which later become enhanced by aggregates of tau. |
| 524 | 24052108 | Phase one can be identified by decreases in Abeta in the CSF, phase 2 by increases of tau in the CSF plus clear evidence of Abeta brain deposits by PET scanning, phase 3 by slight decreases in brain metabolic rate by PET-FDG scanning, phase 4 by slight decreases in brain volume by MRI scanning plus minimal cognitive impairment, phase 5 by increased scanning abnormalities plus clinical diagnosis of AD, and phase 6 by advanced AD requiring institutional care. |
| 525 | 24089686 | Immunocytochemical characterization of Alzheimer disease hallmarks in APP/PS1 transgenic mice treated with a new anti-amyloid-β vaccine. |
| 526 | 24089686 | APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD-like pattern at early ages. |
| 527 | 24089686 | Our findings showed that administration of amyloid-β₁₋₄₂ (Aβ) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before onset of Aβ deposition (7 weeks of age) and/or at an older age (35 weeks of age) is effective in halting the progression and clearing the AD-like neuropathological hallmarks. |
| 528 | 24217510 | Importantly, amyloid deposition is not strongly correlated with cognition in multivariate analyses, unlike hyperphosphorylated tau, neurofibrillary tangles, and synaptic and neuronal loss, which are closely associated with memory deficits. |
| 529 | 24254845 | Both peptides, P13 and P16, could form amyloid fibril structures to potently enhance HIV-1 infectivity. |
| 530 | 24387268 | IGRP and insulin vaccination induce CD8+ T cell-mediated autoimmune diabetes in the RIP-CD80GP mouse. |
| 531 | 24387268 | Of 14 pancreatic proteins tested by DNA vaccination, murine pre-proinsulin 2 (100% of mice; median time after vaccination, 60 days) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (77%, 58 days) could induce diabetes. |
| 532 | 24387268 | Vaccination with DNA encoding for zinc transporter 8, Ia-2, Ia-2β, glutamic acid decarboxylase 67 (Gad67), chromogranin A, insulinoma amyloid polypeptide and homeobox protein Nkx-2.2 induced diabetes development in 25-33% of mice. |
| 533 | 24387268 | Vaccination with DNA encoding for Gad65, secretogranin 5, pancreas/duodenum homeobox protein 1 (Pdx1), carboxyl ester lipase, glucagon and control hepatitis B surface antigen (HBsAg) induced diabetes in <20% of mice. |
| 534 | 24387268 | CD8(+) T cell targets of IGRP were identified with a peptide library-based enzyme-linked immunospot assay, and diabetes could also be induced by vaccination with major histocompatibility complex (MHC) class I-restricted IGRP peptides loaded on mature dendritic cells. |
| 535 | 24525778 | Alzheimer disease (AD) process involves the accumulation of amyloid plaques and tau tangles in the brain, nevertheless the attempts at targeting the main culprits, neurotoxic β-amyloid (Aβ) peptides, have thus far proven unsuccessful for improving cognitive function. |
| 536 | 24534472 | In AD, Pin1 affects two proteins thought to be key to disease pathology: the amyloid precursor protein (APP) and the microtubule-binding protein tau, by switching them from a dysfunctional shape (cis) back to a functional one (trans), which can be distinguished by cis and trans-specific antibodies. |
| 537 | 24534472 | In the brains of people with AD, Pin1 is absent or inactivated and cis tau is accumulated at early stages of AD. |
| 538 | 24534472 | In the absence of Pin1, APP is processed into toxic beta-amyloid and tau becomes misshapen to form tangles. |
| 539 | 25459121 | Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. |
| 540 | 25611858 | Administration of AFFITOPE-vaccines to APP-transgenic mice was found to reduce their cerebral amyloid burden, the associated neuropathological alterations and to improve their cognitive functions. |
| 541 | 25704666 | Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. |
| 542 | 25704666 | Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. |
| 543 | 25748120 | Thus missense, splice site or duplication mutants in the presenilin 1 (PS1), presenilin 2 (PS2) or the amyloid precursor protein (APP) genes, which alter the levels or shift the balance of Aβ produced, are associated with rare, highly penetrant autosomal dominant forms of Familial Alzheimer's Disease (FAD). |
| 544 | 25748120 | Similarly, the more prevalent late-onset forms of AD are associated with both coding and non-coding variants in genes such as SORL1, PICALM and ABCA7 that affect the production and clearance of Aβ. |
| 545 | 25789753 | It is characterized by an imbalance between production and clearance of amyloid β (Aβ) and tau proteins. |
| 546 | 25810517 | Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model. |
| 547 | 25810517 | In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ). |
| 548 | 25810517 | Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model. |
| 549 | 25810517 | In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ). |
| 550 | 25989623 | Molecular characterization of two immunity-related acute-phase proteins: Haptoglobin and serum amyloid A from black rockfish (Sebastes schlegeli). |
| 551 | 25989623 | Haptoglobin (Hp) and serum amyloid A (SAA) are two vital proteins involved in inflammatory reactions and are classified as acute-phase proteins. |
| 552 | 25989623 | Molecular characterization of two immunity-related acute-phase proteins: Haptoglobin and serum amyloid A from black rockfish (Sebastes schlegeli). |
| 553 | 25989623 | Haptoglobin (Hp) and serum amyloid A (SAA) are two vital proteins involved in inflammatory reactions and are classified as acute-phase proteins. |
| 554 | 26182985 | Pentraxins are a family of evolutionary conserved proteins that contains two main members, namely c-reactive proteins (CRPs) and serum amyloid P (SAP), which are involved in acute phase responses in animals. |