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Gene Review

MAPT  -  microtubule-associated protein tau

Homo sapiens

Synonyms: DDPAC, FLJ31424, FTDP-17, MAPTL, MGC138549, ...
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Disease relevance of MAPT


Psychiatry related information on MAPT


High impact information on MAPT


Chemical compound and disease context of MAPT


Biological context of MAPT

  • We show that the entire, fully extended H1 haplotype is associated with PSP, which implicates several other genes in addition to MAPT, as candidate pathogenic loci [2].
  • Direct sequencing of the MAPT exonic sequences in 21 French FTDP families revealed in six index cases the same missense mutation in exon 10 resulting in a Pro-->Leu change at amino acid 301 [19].
  • There was an increased risk of PD for persons with either SNCA 261/261 or MAPT H1/H1 genotypes as compared with persons with neither (odds ratio, 1.96; 95% confidence interval, 1.34-2.86; p = 0.0003) [20].
  • Tau p.A152T significantly increases the risk for both FTD-s [... ORCI=1.6-5.6 ...] and Alzheimer's Disease [... ORCI=1.3-4.2]. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers [21]
  • We examined the promoter region of MAPT and identified single nucleotide polymorphisms and insertions of 1 to 11 nucleotides [22].
  • Our study confirms the notion that the phenotype observed in affected individuals from P301S MAPT mutation families is heterogeneous and is broader than the phenotypes seen to date in affected family members carrying other MAPT mutations [23].

Anatomical context of MAPT

  • The observation of this mutation in several FTDP families might suggest that disruption of binding of MAPT protein to the microtubule is a key event in the pathogenesis of FTDP [19].
  • These findings suggest that the MAPT P301S mutation can cause pathologically subcortical-predominant, neuropil thread-rich, tau-containing lesions, which could result in consistent parkinsonism [23].
  • Microtubule associated protein tau (MAPT) encodes the microtubule associated protein tau, the primary component of neurofibrillary tangles found in Alzheimer's disease and other neurodegenerative disorders [24].
  • NFT is an important sign for the derangement of normal cytoskeletons in degenerating neurons [25].
  • Within the AD group, there was no significant correlation between the ApoE level and SP or neurofibrillary tangle (NFT) counts, either in the hippocampus (r = -0.14 and r = 0.55, respectively), or in the frontal cortex (r = -0.03 and r = 0.01, respectively) [26].

Associations of MAPT with chemical compounds


Physical interactions of MAPT


Enzymatic interactions of MAPT


Regulatory relationships of MAPT


Other interactions of MAPT


Analytical, diagnostic and therapeutic context of MAPT


  1. Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Kraemer, B.C., Zhang, B., Leverenz, J.B., Thomas, J.H., Trojanowski, J.Q., Schellenberg, G.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. The structure of the tau haplotype in controls and in progressive supranuclear palsy. Pittman, A.M., Myers, A.J., Duckworth, J., Bryden, L., Hanson, M., Abou-Sleiman, P., Wood, N.W., Hardy, J., Lees, A., de Silva, R. Hum. Mol. Genet. (2004) [Pubmed]
  3. An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Poorkaj, P., Muma, N.A., Zhukareva, V., Cochran, E.J., Shannon, K.M., Hurtig, H., Koller, W.C., Bird, T.D., Trojanowski, J.Q., Lee, V.M., Schellenberg, G.D. Ann. Neurol. (2002) [Pubmed]
  4. Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Wen, Y., Yang, S.H., Liu, R., Perez, E.J., Brun-Zinkernagel, A.M., Koulen, P., Simpkins, J.W. Biochim. Biophys. Acta (2007) [Pubmed]
  5. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Brion, J.P., Couck, A.M. Am. J. Pathol. (1995) [Pubmed]
  6. Saitohin gene is not associated with Alzheimer's disease. Streffer, J.R., Papassotiropoulos, A., Kurosinski, P., Signorell, A., Wollmer, M.A., Tsolaki, M., Iakovidou, V., Hörndli, F., Bosset, J., Götz, J., Nitsch, R.M., Hock, C. J. Neurol. Neurosurg. Psychiatr. (2003) [Pubmed]
  7. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Shaw-Smith, C., Pittman, A.M., Willatt, L., Martin, H., Rickman, L., Gribble, S., Curley, R., Cumming, S., Dunn, C., Kalaitzopoulos, D., Porter, K., Prigmore, E., Krepischi-Santos, A.C., Varela, M.C., Koiffmann, C.P., Lees, A.J., Rosenberg, C., Firth, H.V., de Silva, R., Carter, N.P. Nat. Genet. (2006) [Pubmed]
  8. Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies. Ramakrishnan, P., Dickson, D.W., Davies, P. Neurobiol. Dis. (2003) [Pubmed]
  9. A prospective study of CSF markers in 250 patients with possible Creutzfeldt-Jakob disease. Van Everbroeck, B., Quoilin, S., Boons, J., Martin, J.J., Cras, P. J. Neurol. Neurosurg. Psychiatr. (2003) [Pubmed]
  10. A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Koolen, D.A., Vissers, L.E., Pfundt, R., de Leeuw, N., Knight, S.J., Regan, R., Kooy, R.F., Reyniers, E., Romano, C., Fichera, M., Schinzel, A., Baumer, A., Anderlid, B.M., Schoumans, J., Knoers, N.V., van Kessel, A.G., Sistermans, E.A., Veltman, J.A., Brunner, H.G., de Vries, B.B. Nat. Genet. (2006) [Pubmed]
  11. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Lu, P.J., Wulf, G., Zhou, X.Z., Davies, P., Lu, K.P. Nature (1999) [Pubmed]
  12. Apolipoprotein E and Alzheimer's disease. Strittmatter, W.J., Roses, A.D. Annu. Rev. Neurosci. (1996) [Pubmed]
  13. Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer's disease. Wang, J.Z., Grundke-Iqbal, I., Iqbal, K. Nat. Med. (1996) [Pubmed]
  14. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F. Nature (1995) [Pubmed]
  15. The amyloid precursor protein of Alzheimer's disease and the Abeta peptide. Storey, E., Cappai, R. Neuropathol. Appl. Neurobiol. (1999) [Pubmed]
  16. Troglitazone, a peroxisome proliferator-activated receptor-gamma agonist, decreases tau phosphorylation in CHOtau4R cells. d'Abramo, C., Ricciarelli, R., Pronzato, M.A., Davies, P. J. Neurochem. (2006) [Pubmed]
  17. Parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model. Klein, R.L., Dayton, R.D., Henderson, K.M., Petrucelli, L. Neurosci. Lett. (2006) [Pubmed]
  18. Tau pathology in a case of familial Alzheimer's disease with a valine to glycine mutation at position 717 in the amyloid precursor protein. Hanger, D.P., Mann, D.M., Neary, D., Anderton, B.H. Neurosci. Lett. (1992) [Pubmed]
  19. Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Dumanchin, C., Camuzat, A., Campion, D., Verpillat, P., Hannequin, D., Dubois, B., Saugier-Veber, P., Martin, C., Penet, C., Charbonnier, F., Agid, Y., Frebourg, T., Brice, A. Hum. Mol. Genet. (1998) [Pubmed]
  20. Interaction of alpha-synuclein and tau genotypes in Parkinson's disease. Mamah, C.E., Lesnick, T.G., Lincoln, S.J., Strain, K.J., de Andrade, M., Bower, J.H., Ahlskog, J.E., Rocca, W.A., Farrer, M.J., Maraganore, D.M. Ann. Neurol. (2005) [Pubmed]
  21. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases. Coppola, G., Chinnathambi, S., Lee, J.J., Dombroski, B.A., Baker, M.C., Soto-Ortolaza, A.I., Lee, S.E., Klein, E., Huang, A.Y., Sears, R., Lane, J.R., Karydas, A.M., Kenet, R.O., Biernat, J., Wang, L.S., Cotman, C.W., Decarli, C.S., Levey, A.I., Ringman, J.M., Mendez, M.F., Chui, H.C., Le Ber, I., Brice, A., Lupton, M.K., Preza, E., Lovestone, S., Powell, J., Graff-Radford, N., Petersen, R.C., Boeve, B.F., Lippa, C.F., Bigio, E.H., Mackenzie, I., Finger, E., Kertesz, A., Caselli, R.J., Gearing, M., Juncos, J.L., Ghetti, B., Spina, S., Bordelon, Y.M., Tourtellotte, W.W., Frosch, M.P., Vonsattel, J.P., Zarow, C., Beach, T.G., Albin, R.L., Lieberman, A.P., Lee, V.M., Trojanowski, J.Q., Van Deerlin, V.M., Bird, T.D., Galasko, D.R., Masliah, E., White, C.L., Troncoso, J.C., Hannequin, D., Boxer, A.L., Geschwind, M.D., Kumar, S., Mandelkow, E.M., Wszolek, Z.K., Uitti, R.J., Dickson, D.W., Haines, J.L., Mayeux, R., Pericak-Vance, M.A., Farrer, L.A., Ross, O.A., Rademakers, R., Schellenberg, G.D., Miller, B.L., Mandelkow, E., Geschwind, D.H. Hum. Mol. Genet. (2012) [Pubmed]
  22. Tau haplotypes regulate transcription and are associated with Parkinson's disease. Kwok, J.B., Teber, E.T., Loy, C., Hallupp, M., Nicholson, G., Mellick, G.D., Buchanan, D.D., Silburn, P.A., Schofield, P.R. Ann. Neurol. (2004) [Pubmed]
  23. Phenotypic heterogeneity within a new family with the MAPT p301s mutation. Yasuda, M., Nakamura, Y., Kawamata, T., Kaneyuki, H., Maeda, K., Komure, O. Ann. Neurol. (2005) [Pubmed]
  24. A genomic sequence analysis of the mouse and human microtubule-associated protein tau. Poorkaj, P., Kas, A., D'Souza, I., Zhou, Y., Pham, Q., Stone, M., Olson, M.V., Schellenberg, G.D. Mamm. Genome (2001) [Pubmed]
  25. Apolipoprotein E in progressive supranuclear palsy in Japan. Sawa, A., Amano, N., Yamada, N., Kajio, H., Yagishita, S., Takahashi, T., Oda, M., Arai, N., Ikeda, K., Tadokoro, M., Matsushita, M. Mol. Psychiatry (1997) [Pubmed]
  26. A quantitative and immunohistochemical study on apolipoprotein E in brain tissue in Alzheimer's disease. Hesse, C., Bogdanovic, N., Davidsson, P., Blennow, K. Dementia and geriatric cognitive disorders. (1999) [Pubmed]
  27. Apolipoprotein E and beta A4-amyloid: signals and effects. Ohm, T.G., Hamker, U., Cedazo-Minguez, A., Röckl, W., Scharnagl, H., März, W., Cowburn, R., Müller, W., Meske, V. Biochem. Soc. Symp. (2001) [Pubmed]
  28. Aluminum modifies the properties of Alzheimer's disease PHF tau proteins in vivo and in vitro. Shin, R.W., Lee, V.M., Trojanowski, J.Q. J. Neurosci. (1994) [Pubmed]
  29. The Ca2+ signaling capacity of the beta 2-integrin on HL60-granulocytic cells is abrogated following phosphorylation of its CD18-chain: relation to impaired protein tyrosine phosphorylation. Hellberg, C., Eierman, D., Sjölander, A., Andersson, T. Exp. Cell Res. (1995) [Pubmed]
  30. Actin dynamics in human neutrophils during adhesion and phagocytosis is controlled by changes in intracellular free calcium. Bengtsson, T., Jaconi, M.E., Gustafson, M., Magnusson, K.E., Theler, J.M., Lew, D.P., Stendahl, O. Eur. J. Cell Biol. (1993) [Pubmed]
  31. Mutations in tau gene exon 10 associated with FTDP-17 alter the activity of an exonic splicing enhancer to interact with Tra2 beta. Jiang, Z., Tang, H., Havlioglu, N., Zhang, X., Stamm, S., Yan, R., Wu, J.Y. J. Biol. Chem. (2003) [Pubmed]
  32. Identification of sequence variants and analysis of the role of the glycogen synthase kinase 3 beta gene and promoter in late onset Alzheimer's disease. Russ, C., Lovestone, S., Powell, J.F. Mol. Psychiatry (2001) [Pubmed]
  33. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Woods, Y.L., Cohen, P., Becker, W., Jakes, R., Goedert, M., Wang, X., Proud, C.G. Biochem. J. (2001) [Pubmed]
  34. Amyloid-beta and tau proteins as biochemical markers of Alzheimer's disease. Sobów, T., Flirski, M., Liberski, P.P. Acta neurobiologiae experimentalis. (2004) [Pubmed]
  35. p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]. Goedert, M., Cohen, E.S., Jakes, R., Cohen, P. FEBS Lett. (1992) [Pubmed]
  36. Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. An, W.L., Cowburn, R.F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.G., Winblad, B., Pei, J.J. Am. J. Pathol. (2003) [Pubmed]
  37. Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Takashima, A., Murayama, M., Murayama, O., Kohno, T., Honda, T., Yasutake, K., Nihonmatsu, N., Mercken, M., Yamaguchi, H., Sugihara, S., Wolozin, B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  38. Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. Huang, Y., Liu, X.Q., Wyss-Coray, T., Brecht, W.J., Sanan, D.A., Mahley, R.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  39. Modulation of beta-amyloid production and fibrillization. Allsop, D., Twyman, L.J., Davies, Y., Moore, S., York, A., Swanson, L., Soutar, I. Biochem. Soc. Symp. (2001) [Pubmed]
  40. Elevated transglutaminase-induced bonds in PHF tau in Alzheimer's disease. Norlund, M.A., Lee, J.M., Zainelli, G.M., Muma, N.A. Brain Res. (1999) [Pubmed]
  41. The impact of different presenilin 1 andpresenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: evidence for other phenotype-modifying factors. Gómez-Isla, T., Growdon, W.B., McNamara, M.J., Nochlin, D., Bird, T.D., Arango, J.C., Lopera, F., Kosik, K.S., Lantos, P.L., Cairns, N.J., Hyman, B.T. Brain (1999) [Pubmed]
  42. Childhood onset in familial prion disease with a novel mutation in the PRNP gene. Rogaeva, E., Zadikoff, C., Ponesse, J., Schmitt-Ulms, G., Kawarai, T., Sato, C., Salehi-Rad, S., St George-Hyslop, P., Lang, A.E. Arch. Neurol. (2006) [Pubmed]
  43. Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis. Carter, C.J. Neurochem. Int. (2007) [Pubmed]
  44. Amyloid beta protein deposition in patients with frontotemporal lobar degeneration: relationship to age and apolipoprotein E genotype. Mann, D.M., McDonagh, A.M., Pickering-Brown, S.M., Kowa, H., Iwatsubo, T. Neurosci. Lett. (2001) [Pubmed]
  45. A cDNA for a human microtubule associated protein 2 epitope in the Alzheimer neurofibrillary tangle. Neve, R.L., Selkoe, D.J., Kurnit, D.M., Kosik, K.S. Brain Res. (1986) [Pubmed]
  46. New immunoassay for the mapping of neurofibrillary degeneration in Alzheimer's disease using two monoclonal antibodies against human paired helical filament tau proteins. Condamines, O., Buée-Scherrer, V., Boissier, L., Wattez, A., Delacourte, A., Pau, B., Mourton-Gilles, C. Neurosci. Lett. (1995) [Pubmed]
  47. The microtubule associated protein Tau gene and Alzheimer's disease--an association study and meta-analysis. Russ, C., Powell, J.F., Zhao, J., Baker, M., Hutton, M., Crawford, F., Mullan, M., Roks, G., Cruts, M., Lovestone, S. Neurosci. Lett. (2001) [Pubmed]
  48. alpha-synuclein binds to Tau and stimulates the protein kinase A-catalyzed tau phosphorylation of serine residues 262 and 356. Jensen, P.H., Hager, H., Nielsen, M.S., Hojrup, P., Gliemann, J., Jakes, R. J. Biol. Chem. (1999) [Pubmed]
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