Ignet

Gene Information

Gene symbol: MAPT

Gene name: microtubule-associated protein tau

HGNC ID: 6893

Synonyms: MTBT1, tau, PPND, FTDP-17, TAU, MSTD, MTBT2, FLJ31424, MGC138549

Related Genes

#	Gene Symbol	Number of hits
1	APLP2	1 hits
2	APOE	1 hits
3	APP	1 hits
4	CD34	1 hits
5	CISH	1 hits
6	IFNG	1 hits
7	IL1B	1 hits
8	IL2	1 hits
9	INS	1 hits
10	JUN	1 hits
11	LAMP1	1 hits
12	LPAL2	1 hits
13	MAPK14	1 hits
14	MAPK8	1 hits
15	MAPK9	1 hits
16	PIN1	1 hits
17	POLD4	1 hits
18	PSEN1	1 hits
19	SNCA	1 hits
20	SOD1	1 hits
21	SUCLG2	1 hits
22	TNF	1 hits
23	YWHAQ	1 hits
24	ZNF274	1 hits

Related Sentences

#	PMID	Sentence
1	9079741	The analysis showed high expression of interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha, IL-2, and interferon (IFN)-tau in BCG (7/7, 7/7, 7/7, 5/7) and N-CWS (9/9, 9/9, 8/9, 8/9) treated tumors in comparison to low expression in controls (3/9, 0/9, 3/9, 3/9).
2	11281812	Efforts to treat the underlying pathology are based on modulation of APP processing in order to decrease the accumulation of beta-amyloid, those to decrease tau hyperphosphorylation, use of nerve growth factors and those based on Apo-E modulation.
3	12050010	A peptide derived from ZF1 had a higher quantum yield and longer average lifetime (tau) than ZF2.
4	12050010	BLV p12 tau and rotational correlation time were greater than ZF values, but all de-metallated sequences gave similar results.
5	12050010	A peptide derived from ZF1 had a higher quantum yield and longer average lifetime (tau) than ZF2.
6	12050010	BLV p12 tau and rotational correlation time were greater than ZF values, but all de-metallated sequences gave similar results.
7	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.
8	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.
9	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.
10	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.
11	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.
12	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.
13	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).
14	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.
15	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.
16	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.
17	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.
18	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).
19	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.
20	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.
21	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.
22	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.
23	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.
24	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.
25	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.
26	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.
27	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.
28	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.
29	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.
30	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.
31	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.
32	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.
33	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.
34	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.
35	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.
36	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.
37	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.
38	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.
39	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.
40	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.
41	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.
42	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.
43	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.
44	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.
45	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.
46	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.
47	15294135	Clearing tau pathology with Abeta immunotherapy--reversible and irreversible stages revealed.
48	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).
49	15294135	Clearing tau pathology with Abeta immunotherapy--reversible and irreversible stages revealed.
50	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).
51	15294141	Using a triple transgenic model (3xTg-AD) that develops both lesions in AD-relevant brain regions, we determined the consequence of Abeta clearance on the development of tau pathology.
52	15294141	Here we show that Abeta immunotherapy reduces not only extracellular Abeta plaques but also intracellular Abeta accumulation and most notably leads to the clearance of early tau pathology.
53	15294141	We find that Abeta deposits are cleared first and subsequently reemerge prior to the tau pathology, indicative of a hierarchical and direct relationship between Abeta and tau.
54	15294141	The clearance of the tau pathology is mediated by the proteasome and is dependent on the phosphorylation state of tau, as hyperphosphorylated tau aggregates are unaffected by the Abeta antibody treatment.
55	15294141	Using a triple transgenic model (3xTg-AD) that develops both lesions in AD-relevant brain regions, we determined the consequence of Abeta clearance on the development of tau pathology.
56	15294141	Here we show that Abeta immunotherapy reduces not only extracellular Abeta plaques but also intracellular Abeta accumulation and most notably leads to the clearance of early tau pathology.
57	15294141	We find that Abeta deposits are cleared first and subsequently reemerge prior to the tau pathology, indicative of a hierarchical and direct relationship between Abeta and tau.
58	15294141	The clearance of the tau pathology is mediated by the proteasome and is dependent on the phosphorylation state of tau, as hyperphosphorylated tau aggregates are unaffected by the Abeta antibody treatment.
59	15294141	Using a triple transgenic model (3xTg-AD) that develops both lesions in AD-relevant brain regions, we determined the consequence of Abeta clearance on the development of tau pathology.
60	15294141	Here we show that Abeta immunotherapy reduces not only extracellular Abeta plaques but also intracellular Abeta accumulation and most notably leads to the clearance of early tau pathology.
61	15294141	We find that Abeta deposits are cleared first and subsequently reemerge prior to the tau pathology, indicative of a hierarchical and direct relationship between Abeta and tau.
62	15294141	The clearance of the tau pathology is mediated by the proteasome and is dependent on the phosphorylation state of tau, as hyperphosphorylated tau aggregates are unaffected by the Abeta antibody treatment.
63	15294141	Using a triple transgenic model (3xTg-AD) that develops both lesions in AD-relevant brain regions, we determined the consequence of Abeta clearance on the development of tau pathology.
64	15294141	Here we show that Abeta immunotherapy reduces not only extracellular Abeta plaques but also intracellular Abeta accumulation and most notably leads to the clearance of early tau pathology.
65	15294141	We find that Abeta deposits are cleared first and subsequently reemerge prior to the tau pathology, indicative of a hierarchical and direct relationship between Abeta and tau.
66	15294141	The clearance of the tau pathology is mediated by the proteasome and is dependent on the phosphorylation state of tau, as hyperphosphorylated tau aggregates are unaffected by the Abeta antibody treatment.
67	16914852	The identification of disease-causing mutations in proteins such as amyloid-beta precursor protein (betaAPP) and presenilin1 (PS1), together with the discovery of other high risk factors (e.g., Apolipoprotein E4), as well as pathogenic mutations in the tau protein has led to the creation of several transgenic mice, including those expressing bi- and tri-genic constructs.
68	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.
69	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.
70	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.
71	17076654	Therapies that alter Abeta and tau through these various targets are likely to have significant disease modifying effects.
72	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.
73	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.
74	17076654	Therapies that alter Abeta and tau through these various targets are likely to have significant disease modifying effects.
75	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.
76	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.
77	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.
78	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.
79	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.
80	17344945	This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.
81	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.
82	18819685	The brain lesions associated with Alzheimer's disease are caused by extracellular accumulation of Abeta peptide and intracellular accumulation of tau protein.
83	18819685	The Abeta deposits first involve the neocortex, while the tau pathology is initially found in the hippocampal region.
84	18819685	Mutations of APP, the precursor of Abeta peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a cascade of reactions link Abeta overproduction, tau pathology and the clinical phenotype.
85	18819685	The brain lesions associated with Alzheimer's disease are caused by extracellular accumulation of Abeta peptide and intracellular accumulation of tau protein.
86	18819685	The Abeta deposits first involve the neocortex, while the tau pathology is initially found in the hippocampal region.
87	18819685	Mutations of APP, the precursor of Abeta peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a cascade of reactions link Abeta overproduction, tau pathology and the clinical phenotype.
88	18819685	The brain lesions associated with Alzheimer's disease are caused by extracellular accumulation of Abeta peptide and intracellular accumulation of tau protein.
89	18819685	The Abeta deposits first involve the neocortex, while the tau pathology is initially found in the hippocampal region.
90	18819685	Mutations of APP, the precursor of Abeta peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a cascade of reactions link Abeta overproduction, tau pathology and the clinical phenotype.
91	18819689	Alzheimer's disease is characterized by two main lesions: amyloid plaques and neurofibrillary tangles composed of aggregated A Beta peptides and hyperphosphorylated tau.
92	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.
93	19482462	More recently, alternative approaches have begun to target the microtubule binding protein tau, a component of neurofibrillary tangles.
94	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).
95	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.
96	19553436	These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits.
97	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.
98	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.
99	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).
100	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.
101	19553436	These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits.
102	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.
103	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.
104	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).
105	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.
106	19553436	These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits.
107	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.
108	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.
109	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).
110	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.
111	19553436	These mice show amyloid pathology, hyperphosphorylated and aggregated normal mouse tau, significant neuron loss, and cognitive deficits.
112	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.
113	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.
114	20205639	Moreover, if Abeta pathology drives tau pathology as reported in several transgenic animal models, and once established if tau pathology can become self propagating, then early intervention with anti-Abeta immunotherapy may be critical for favorable clinical outcomes.
115	20471477	In AD, the normal soluble amyloid beta (sAbeta) peptide is converted into oligomeric/fibrillar Abeta.
116	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.
117	20471477	Perhaps the most exciting of the therapeutic approaches being developed is immunomodulation targeting the aggregating proteins, Abeta and tau.
118	20567751	Although cerebrospinal fluid (CSF) Abeta and tau protein levels are candidate biomarkers for AD, the invasive sampling procedure with associated complications limits their use in routine clinical practice.
119	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.
120	20632020	Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques.
121	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.
122	20632020	There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta.
123	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.
124	20675870	Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons.
125	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.
126	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.
127	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.
128	20675870	Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons.
129	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.
130	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.
131	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.
132	20675870	Immunohistochemical studies with antibodies to tau and Abeta revealed that extracellular accumulation of Abeta precedes that of tau in neurons.
133	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.
134	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.
135	20980799	The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer's disease (AD) and many neurodegenerative diseases.
136	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.
137	22461630	Aggregation of the microtubule associated protein Tau is associated with several neurodegenerative disorders, including Alzheimer disease and frontotemporal dementia.
138	23154634	Cis phosphorylated tau as the earliest detectable pathogenic conformation in Alzheimer disease, offering novel diagnostic and therapeutic strategies.
139	23486963	The Alzheimer's disease (AD) process is understood to involve the accumulation of amyloid plaques and tau tangles in the brain.
140	23725605	AD pathogenesis has been associated with the accumulation, aggregation, and deposition of amyloid beta (Abeta) peptides in the brain.
141	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.
142	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.
143	23861639	Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date.
144	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.
145	24052108	AD probably results from the inflammatory response induced by extracellular Abeta deposits, which later become enhanced by aggregates of tau.
146	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.
147	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.
148	24052108	AD probably results from the inflammatory response induced by extracellular Abeta deposits, which later become enhanced by aggregates of tau.
149	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.
150	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.
151	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.
152	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.
153	24534472	In the brains of people with AD, Pin1 is absent or inactivated and cis tau is accumulated at early stages of AD.
154	24534472	In the absence of Pin1, APP is processed into toxic beta-amyloid and tau becomes misshapen to form tangles.
155	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.
156	24534472	In the brains of people with AD, Pin1 is absent or inactivated and cis tau is accumulated at early stages of AD.
157	24534472	In the absence of Pin1, APP is processed into toxic beta-amyloid and tau becomes misshapen to form tangles.
158	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.
159	24534472	In the brains of people with AD, Pin1 is absent or inactivated and cis tau is accumulated at early stages of AD.
160	24534472	In the absence of Pin1, APP is processed into toxic beta-amyloid and tau becomes misshapen to form tangles.
161	25214033	The asialoglycoprotein receptor (ASGPR) is a high-capacity C-type lectin receptor expressed on mammalian hepatocytes.
162	25214033	Proteoglycans (PGs), a core protein and glycosaminoglycans (GAGs) chain, play important roles in amyloid-beta protein as well as tau processing, and have potential significance in Alzheimer's disease (AD) therapy.
163	25430817	Data were corrected for age, gender, duration of dementia and APOE genotype and also assessed in relation to Aβ42 and tau pathology and key features of AD.
164	25430817	In AD, associations of spongiosis status, curvature ratio and pPKR load with microglial markers Iba1, CD68 and CD32 suggest a role for microglia in neurodegeneration.
165	25430817	After immunization, correlations were detected between the number of NeuN-positive neurons and pPKR with Iba1, CD68 and CD64, suggesting that microglia are involved in the neuronal loss.
166	25459121	Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology.
167	25676491	Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies.
168	25789753	It is characterized by an imbalance between production and clearance of amyloid β (Aβ) and tau proteins.
169	25810517	Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model.
170	25810517	In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ).
171	25810517	Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer's disease mouse model.
172	25810517	In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect of amyloid β protein (Aβ).