tau

Summary

Gene Symbol: tau
Description: microtubule associated protein tau
Alias: DDPAC, FTDP-17, MAPTL, MSTD, MTBT1, MTBT2, PPND, PPP1R103, TAU, microtubule-associated protein tau, G protein beta1/gamma2 subunit-interacting factor 1, PHF-tau, neurofibrillary tangle protein, paired helical filament-tau, protein phosphatase 1, regulatory subunit 103
Species: human

Top Publications

  1. doi Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney NSW 2050, Australia
    Cell 142:387-97. 2010
  2. pmc Trans-synaptic spread of tau pathology in vivo
    Li Liu
    Department of Pathology and Cell Biology, Taub Institute for Alzheimer s Disease Research, Columbia University, New York, New York, United States of America
    PLoS ONE 7:e31302. 2012
  3. ncbi Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
    M Goedert
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, England
    Neuron 3:519-26. 1989
  4. pmc Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21
    Chris C A Spencer
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Hum Mol Genet 20:345-53. 2011
  5. pmc Genome-wide association study reveals genetic risk underlying Parkinson's disease
    Javier Simon-Sanchez
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 41:1308-12. 2009
  6. ncbi CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
    Leonard Petrucelli
    Mayo Clinic, Jacksonville, FL 32224, USA
    Hum Mol Genet 13:703-14. 2004
  7. ncbi The role of tau (MAPT) in frontotemporal dementia and related tauopathies
    R Rademakers
    Department of Molecular Genetics, Neurogenetics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 24:277-95. 2004
  8. doi In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons
    Tara L Spires-Jones
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 28:862-7. 2008
  9. ncbi GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila
    A Mudher
    Department of Neuroscience and Old Age Psychiatry, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
    Mol Psychiatry 9:522-30. 2004
  10. pmc Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
    Alexis Elbaz
    INSERM, U708, Neuroepidemiology, F 75013, Paris, France
    Ann Neurol 69:778-92. 2011

Research Grants

  1. Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors for
    ALAN D SNOW; Fiscal Year: 2011
  2. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
  3. Marc I Diamond; Fiscal Year: 2014
  4. Canonical Wnt Signaling by the Proteolytc Processing of LRP6
    BRANDON RICHARD BEAGLE; Fiscal Year: 2010
  5. Gloria Lee; Fiscal Year: 2016
  6. Genomic Analysis of Alzheimer's Disease Genes
    GERARD DAVID SCHELLENBERG; Fiscal Year: 2013
  7. Carlos Cruchaga; Fiscal Year: 2016
  8. David Morgan; Fiscal Year: 2015
  9. Hillel Grossman; Fiscal Year: 2014
  10. A Model of Early Alzheimer Disease
    Bradley T Hyman; Fiscal Year: 2012

Detail Information

Publications466 found, 100 shown here

  1. doi Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney NSW 2050, Australia
    Cell 142:387-97. 2010
    Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) and tau deposition in brain. It has emerged that Abeta toxicity is tau dependent, although mechanistically this link remains unclear...
  2. pmc Trans-synaptic spread of tau pathology in vivo
    Li Liu
    Department of Pathology and Cell Biology, Taub Institute for Alzheimer s Disease Research, Columbia University, New York, New York, United States of America
    PLoS ONE 7:e31302. 2012
    ..connected circuits, we have generated a transgenic mouse model that differentially expresses pathological human tau in the EC and we have examined the distribution of tau pathology at different timepoints...
  3. ncbi Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
    M Goedert
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, England
    Neuron 3:519-26. 1989
    We have determined the sequences of isoforms of human tau protein, which differ from previously reported forms by insertions of 29 or 58 amino acids in the amino-terminal region...
  4. pmc Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21
    Chris C A Spencer
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Hum Mol Genet 20:345-53. 2011
    ..We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease...
  5. pmc Genome-wide association study reveals genetic risk underlying Parkinson's disease
    Javier Simon-Sanchez
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 41:1308-12. 2009
    ..14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease...
  6. ncbi CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
    Leonard Petrucelli
    Mayo Clinic, Jacksonville, FL 32224, USA
    Hum Mol Genet 13:703-14. 2004
    ..g. tau and alpha-synuclein respectively)...
  7. ncbi The role of tau (MAPT) in frontotemporal dementia and related tauopathies
    R Rademakers
    Department of Molecular Genetics, Neurogenetics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mutat 24:277-95. 2004
    b>Tau is a multifunctional protein that was originally identified as a microtubule-associated protein...
  8. doi In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons
    Tara L Spires-Jones
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurosci 28:862-7. 2008
    ..Finally, histochemical assessments revealed evidence of caspase-cleaved tau, but no TUNEL (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling) positive or ..
  9. ncbi GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila
    A Mudher
    Department of Neuroscience and Old Age Psychiatry, Institute of Psychiatry, Kings College London, De Crespigny Park, London, UK
    Mol Psychiatry 9:522-30. 2004
    The tauopathies are a group of disorders characterised by aggregation of the microtubule-associated protein tau and include Alzheimer's disease (AD) and the fronto-temporal dementias (FTD)...
  10. pmc Independent and joint effects of the MAPT and SNCA genes in Parkinson disease
    Alexis Elbaz
    INSERM, U708, Neuroepidemiology, F 75013, Paris, France
    Ann Neurol 69:778-92. 2011
    ..the independent and joint effects of the genes encoding alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) in Parkinson disease (PD) as part of a large meta-analysis of individual data from case-control studies ..
  11. ncbi The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein
    P J Lu
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 399:784-8. 1999
    ..tangle, which contains paired helical filaments (PHFs) composed of the microtubule-associated protein tau. Tau is hyperphosphorylated in PHFs, and phosphorylation of tau abolishes its ability to bind microtubules and ..
  12. pmc Tau suppression in a neurodegenerative mouse model improves memory function
    K SantaCruz
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    Science 309:476-81. 2005
    ..Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments...
  13. pmc LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth
    Fumitaka Kawakami
    Department of Biochemistry, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan
    PLoS ONE 7:e30834. 2012
    ..In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) ..
  14. pmc PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    FEBS Lett 580:6269-74. 2006
    Phosphorylation of tau protein is regulated by several kinases, especially glycogen synthase kinase 3beta (GSK-3beta), cyclin-dependent protein kinase 5 (cdk5) and cAMP-dependent protein kinase (PKA)...
  15. pmc Nuclear tau, a key player in neuronal DNA protection
    Audrey Sultan
    Inserm UMR837, Alzheimer and Tauopathies, 1 rue Michel Polonovski, 59045 Lille, France
    J Biol Chem 286:4566-75. 2011
    b>Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells...
  16. pmc A protein factor essential for microtubule assembly
    M D Weingarten
    Proc Natl Acad Sci U S A 72:1858-62. 1975
    A heat stable protein essentail for microtubule assembly has been isolated. This protein, which we designate tau (tau), is present in association with tubulin purified from porcine brain by repeated cycles of polymerization...
  17. doi Gene expression of estrogen receptor, progesterone receptor and microtubule-associated protein Tau in high-risk early breast cancer: a quest for molecular predictors of treatment benefit in the context of a Hellenic Cooperative Oncology Group trial
    George Pentheroudakis
    Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece
    Breast Cancer Res Treat 116:131-43. 2009
    ..We sought to study the predictive significance and correlations of transcriptional profiling of the ER, PgR and microtubule-associated protein Tau (MAP-Tau) genes in early breast cancer.
  18. ncbi Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins--a role in nuclear localization
    Tony Lefebvre
    Laboratoire de Chimie Biologique, Unité Mixte de Recherches 8576 du CNRS, Université des Sciences et Technologies de Lille I, F 59655 Villeneuve d Ascq, France
    Biochim Biophys Acta 1619:167-76. 2003
    Both phosphorylation and O-GlcNAc glycosylation posttranslationally modify microtubule-associated Tau proteins...
  19. ncbi Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and alpha-synuclein
    Veronique Dorval
    Department of Medical Biophysics and Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ontario M5S 3H2, Canada
    J Biol Chem 281:9919-24. 2006
    ..We have examined the covalent attachment of the small ubiquitin-like modifier (SUMO) proteins to tau and alpha-synuclein, two natively unfolded proteins that define several neurodegenerative diseases...
  20. ncbi Accumulation of pathological tau species and memory loss in a conditional model of tauopathy
    Zdenek Berger
    Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
    J Neurosci 27:3650-62. 2007
    ..This suggests that NFTs are not the major neurotoxic tau species, at least during the early stages of pathogenesis...
  21. pmc Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations
    Jonathan D Rohrer
    Dementia Research Centre, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK
    Neuroimage 53:1070-6. 2010
    ..Nine patients with progranulin (GRN) mutations and eleven patients with microtubule-associated protein tau (MAPT) mutations had T1 MR brain imaging...
  22. pmc Pseudohyperphosphorylation has differential effects on polymerization and function of tau isoforms
    Benjamin Combs
    Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045, United States
    Biochemistry 50:9446-56. 2011
    The microtubule-associated protein tau exists as six isoforms created through the splicing of the second, third, and tenth exons...
  23. pmc The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system
    Hwan Ching Tai
    MassGeneral Institute of Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Am J Pathol 181:1426-35. 2012
    ..Tangles are composed of misfolded hyperphosphorylated tau proteins; however, the link between tau abnormalities and synaptic dysfunction remains unclear...
  24. doi Tau and p-tau as CSF biomarkers in dementia: a meta-analysis
    Argonde C van Harten
    Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
    Clin Chem Lab Med 49:353-66. 2011
    To evaluate the value of total tau (tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) in the differential diagnosis of dementia, more specifically: dementia with Lewy Bodies (DLB), frontotemporal lobar degeneration (FTLD), ..
  25. doi Alzheimer disease-like clinical phenotype in a family with FTDP-17 caused by a MAPT R406W mutation
    S G Lindquist
    Memory Disorders Research Group, The Neuroscience Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
    Eur J Neurol 15:377-85. 2008
    ..a clinical phenotype resembling Alzheimer's disease and a pathogenic mutation (R406W) in the microtubule associated protein tau (MAPT) gene...
  26. doi Direct analysis of tau from PSP brain identifies new phosphorylation sites and a major fragment of N-terminally cleaved tau containing four microtubule-binding repeats
    Selina Wray
    MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, London, UK
    J Neurochem 105:2343-52. 2008
    Tangles containing hyperphosphorylated aggregates of insoluble tau are a pathological hallmark of progressive supranuclear palsy (PSP)...
  27. pmc Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 85:4051-5. 1988
    ..This protein is highly homologous to the sequence of the mouse microtubule-associated protein tau and thus constitutes the human equivalent of mouse tau...
  28. ncbi Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau
    O Bugiani
    Istituto Neurologico Carlo Besta, Milano, Italy
    J Neuropathol Exp Neurol 58:667-77. 1999
    The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families...
  29. pmc The frontotemporal dementia mutation R406W blocks tau's interaction with the membrane in an annexin A2-dependent manner
    Anne Gauthier-Kemper
    Department of Neurobiology, University of Osnabruck, Osnabruck, Germany
    J Cell Biol 192:647-61. 2011
    Changes of the microtubule-associated protein tau are central in Alzheimer's disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17)...
  30. pmc Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration
    Alejandra D Alonso
    Department of Biology and Center for Developmental Neuroscience, College of Staten Island, and The Graduate Center, The City University of New York, New York 10314, USA
    J Biol Chem 285:30851-60. 2010
    Abnormal hyperphosphorylation of the microtubule-associated protein Tau is a hallmark of Alzheimer disease and related diseases called tauopathies...
  31. ncbi p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 312:95-9. 1992
    ..Here we show that p42 MAP kinase phosphorylates recombinant tau and converts it to a form which is similar to PHF tau. Of the major serine/threonine protein phosphatases found in mammalian tissues only protein phosphatase 2A (PP2A) ..
  32. ncbi Tau cleavage and dephosphorylation in cerebellar granule neurons undergoing apoptosis
    N Canu
    Dipartimento di Neuroscienze, Universita di Roma Tor Vergata, 00173 Roma, Italy
    J Neurosci 18:7061-74. 1998
    ..During this process we found that tau, a neuronal microtubule-associated protein that plays a key role in the maintenance of neuronal architecture, and ..
  33. ncbi Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy
    Bin Zhang
    The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 4283, USA
    J Neurosci 24:4657-67. 2004
    Intracellular accumulations of filamentous tau inclusions are neuropathological hallmarks of neurodegenerative diseases known as tauopathies...
  34. ncbi Haplotype-specific expression of exon 10 at the human MAPT locus
    Tara M Caffrey
    The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
    Hum Mol Genet 15:3529-37. 2006
    Neurofibrillary tangles composed of exon 10+ microtubule associated protein tau (MAPT) deposits are the characteristic feature of the neurodegenerative diseases progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)...
  35. pmc Interaction of tau with the neural plasma membrane mediated by tau's amino-terminal projection domain
    R Brandt
    Institute of Neurobiology, University of Heidelberg, Germany
    J Cell Biol 131:1327-40. 1995
    The neuronal microtubule-associated protein tau is required for the development of cell polarity in cultured neurons...
  36. ncbi Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules
    Guibin Li
    Center for Molecular Neurobiology, Ohio State Biochemistry Program, Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA
    J Biol Chem 279:15938-45. 2004
    b>Tau hyperphosphorylation precedes neuritic lesion formation in Alzheimer's disease, suggesting it participates in the tau fibrillization reaction pathway...
  37. pmc Template-assisted filament growth by parallel stacking of tau
    Martin Margittai
    Department of Biochemistry and Molecular Biology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 2821, USA
    Proc Natl Acad Sci U S A 101:10278-83. 2004
    b>Tau filaments are found in >20 neurodegenerative diseases. Yet, because of their enormous molecular weights and poor tendency to form highly ordered 3D crystal lattices, they have evaded high-resolution structure determination...
  38. ncbi The "jaws" of the tau-microtubule interaction
    Marco D Mukrasch
    Department for NMR based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen
    J Biol Chem 282:12230-9. 2007
    b>Tau is the major microtubule-associated protein in neuronal axons. It aggregates into "neurofibrillary tangles" during the course of Alzheimer disease...
  39. pmc Akt and CHIP coregulate tau degradation through coordinated interactions
    Chad A Dickey
    Department of Molecular Pharmacology and Physiology and H Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA
    Proc Natl Acad Sci U S A 105:3622-7. 2008
    A hallmark of the pathology of Alzheimer's disease is the accumulation of the microtubule-associated protein tau into fibrillar aggregates...
  40. ncbi Tau haplotypes regulate transcription and are associated with Parkinson's disease
    John B J Kwok
    Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia
    Ann Neurol 55:329-34. 2004
    A primary haplotype (H1) of the microtubule-associated protein Tau (MAPT) gene is associated with Parkinson's disease (PD). However, the mechanism for disease susceptibility remains unknown...
  41. ncbi Tyrosine 394 is phosphorylated in Alzheimer's paired helical filament tau and in fetal tau with c-Abl as the candidate tyrosine kinase
    Pascal Derkinderen
    Department of Neuroscience, Institute of Psychiatry, King s College London, London SE5 8AF, United Kingdom
    J Neurosci 25:6584-93. 2005
    b>Tau is a major microtubule-associated protein of axons and is also the principal component of the paired helical filaments (PHFs) that comprise the neurofibrillary tangles found in Alzheimer's disease and other tauopathies...
  42. ncbi The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathy
    Marion Hogg
    Neurogenetics Laboratory, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
    Acta Neuropathol 106:323-36. 2003
    ..At autopsy there was severe atrophy of the frontal and temporal lobes. Tau-positive Pick bodies, which ultrastructurally were composed of straight filaments, were present, accompanied by ..
  43. pmc An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology
    Christian Wider
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    J Neurol Neurosurg Psychiatry 83:424-9. 2012
    ..The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies...
  44. doi Mixed tau, TDP-43 and p62 pathology in FTLD associated with a C9ORF72 repeat expansion and p.Ala239Thr MAPT (tau) variant
    Andrew King
    Department of Clinical Neuropathology, Academic Neuroscience Building, King s College Hospital, Denmark Hill, London SE5 9RS, UK
    Acta Neuropathol 125:303-10. 2013
    ..Ala239Thr variant in MAPT (microtubule associated protein tau) gene not previously associated with tau pathology...
  45. pmc An unbiased approach to identifying tau kinases that phosphorylate tau at sites associated with Alzheimer disease
    Annalisa Cavallini
    Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom
    J Biol Chem 288:23331-47. 2013
    ..the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia...
  46. doi Stimulatory effect of α-synuclein on the tau-phosphorylation by GSK-3β
    Fumitaka Kawakami
    Department of Biochemistry, Kitasato University, Minami Ku, Sagamihara, Japan
    FEBS J 278:4895-904. 2011
    Hyperphosphorylation of tau protein (tau) causes neurodegenerative diseases such as Alzheimer's disease (AD)...
  47. pmc Evidence for two distinct binding sites for tau on microtubules
    Victoria Makrides
    Neuroscience Research Institute, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    Proc Natl Acad Sci U S A 101:6746-51. 2004
    The microtubule-associated protein tau regulates diverse and essential microtubule functions, from the nucleation and promotion of microtubule polymerization to the regulation of microtubule polarity and dynamics, as well as the spacing ..
  48. pmc Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by Tau protein
    Gayathri Ramachandran
    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India
    J Biol Chem 286:38948-59. 2011
    The aggregation of the natively disordered protein, Tau, to form lesions called neurofibrillary tangles is a characteristic feature of several neurodegenerative tauopathies...
  49. pmc Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome
    Jerzy Wegiel
    Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Neuropathol Exp Neurol 70:36-50. 2011
    ..DYRK1A phosphorylates cytoplasmic tau protein and appears in intraneuronal neurofibrillary tangles (NFTs)...
  50. pmc The influence of phospho-τ on dendritic spines of cortical pyramidal neurons in patients with Alzheimer's disease
    Paula Merino-Serrais
    Laboratorio Cajal de Circuitos Corticales CTB, Universidad Politecnica de Madrid, Campus Montegancedo S N, 28223 Pozuelo de Alarcon, Spain
    Brain 136:1913-28. 2013
    ..Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, ..
  51. doi Identification of O-GlcNAc sites within peptides of the Tau protein and their impact on phosphorylation
    Caroline Smet-Nocca
    Unite de Glycobiologie Structurale et Fonctionnelle, CNRS UMR8576, IFR 147, Université de Lille1, 59655 Villeneuve d Ascq cedex, France
    Mol Biosyst 7:1420-9. 2011
    Phosphorylation of the microtubule-associated Tau protein plays a major role in the regulation of its activity of tubulin polymerization and/or stabilization of microtubule assembly...
  52. pmc Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17
    L N Clark
    Department of Neurology and Gallo Clinic and Research Center, University of California, San Francisco, CA 94110, USA
    Proc Natl Acad Sci U S A 95:13103-7. 1998
    Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21-22...
  53. ncbi A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy
    Raquel Ros
    Banco de Tejidos para Investigaciones Neurológicas, Universidad Autonoma de Madrid, Spain
    Arch Neurol 62:1444-50. 2005
    Progressive supranuclear palsy (PSP) is a clinicopathological syndrome related to tau deposits and in linkage disequilibrium with tau polymorphisms. Some rare familial PSP cases have been related to tau gene mutations.
  54. pmc The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family
    Salvatore Spina
    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Brain 131:72-89. 2008
    Multiple system tauopathy with presenile dementia (MSTD) is an inherited disease caused by a (g) to (a) transition at position +3 in intron 10 of Tau...
  55. doi The effect of age and the H1c MAPT haplotype on MAPT expression in human brain
    Jesse B G Hayesmoore
    Neuropsychiatric Genetics Group, Cardiff University School of Medicine, Cardiff, UK
    Neurobiol Aging 30:1652-6. 2009
    ..that the effect of the H1c haplotype relates to an increase in MAPT expression leading to an increase in tau neurofibrillary tangle deposition...
  56. pmc Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro
    Hamid Y Qureshi
    Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada
    J Biol Chem 286:5055-68. 2011
    ..In addition, genome-wide association studies indicate that α-synuclein and Tau protein synergistically increase disease susceptibility in the human population...
  57. pmc RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site
    Amar Kar
    Northwestern University Feinberg School of Medicine, 303 E Superior St, Lurie 6 117, Chicago, IL 60611, USA
    Mol Cell Biol 31:1812-21. 2011
    Regulation of tau exon 10 splicing plays an important role in tauopathy. One of the cis elements regulating tau alternative splicing is a stem-loop structure at the 5' splice site of tau exon 10...
  58. doi Tyrosine phosphorylation of tau regulates its interactions with Fyn SH2 domains, but not SH3 domains, altering the cellular localization of tau
    Alessia Usardi
    Department of Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King s College London, UK
    FEBS J 278:2927-37. 2011
    Recent reports have demonstrated that interactions between the microtubule-associated protein tau and the nonreceptor tyrosine kinase Fyn play a critical role in mediating synaptic toxicity and neuronal loss in response to β-amyloid (Aβ..
  59. pmc HDAC6 mutations rescue human tau-induced microtubule defects in Drosophila
    Ying Xiong
    Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Proc Natl Acad Sci U S A 110:4604-9. 2013
    ..disease (AD) and related tauopathy patients contain neurofibrillary tangles composed of hyperphosphorylated tau protein...
  60. pmc Haplotype-specific expression of the N-terminal exons 2 and 3 at the human MAPT locus
    Tara M Caffrey
    The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Neurobiol Aging 29:1923-9. 2008
    The microtubule-associated protein tau (MAPT) H1 haplotype shows a strong association to the sporadic neurodegenerative diseases, progressive supranuclear palsy and corticobasal degeneration...
  61. doi Increased association between rough endoplasmic reticulum membranes and mitochondria in transgenic mice that express P301L tau
    Sebastien Perreault
    Departement de pathologie et biologie cellulaire, Universite de Montreal, Montreal, Quebec, Canada
    J Neuropathol Exp Neurol 68:503-14. 2009
    In several neurodegenerative diseases, including Alzheimer disease, the neuronal microtubule-associated protein tau becomes hyperphosphorylated, accumulates in the somatodendritic compartment, and aggregates into insoluble filaments...
  62. doi Drosophila models of human tauopathies indicate that Tau protein toxicity in vivo is mediated by soluble cytosolic phosphorylated forms of the protein
    Sébastien Feuillette
    INSERM U614, Rouen Institute for Medical Research, Faculty of Medicine, University of Rouen, Rouen Cedex, France
    J Neurochem 113:895-903. 2010
    b>Tau is a neuronal microtubule-associated protein involved in microtubules assembly and stabilization...
  63. pmc Tau protein binds to microtubules through a flexible array of distributed weak sites
    K A Butner
    Department of Biochemistry, University of California, San Francisco 94143 0448
    J Cell Biol 115:717-30. 1991
    b>Tau protein plays a role in the extension and maintenance of neuronal processes through a direct association with microtubules...
  64. ncbi Clinical features of frontotemporal dementia due to the intronic tau 10(+16) mutation
    J C Janssen
    Dementia Research Group, Institute of Neurology, London, UK
    Neurology 58:1161-8. 2002
    To describe the clinical features of nine British families with neuropathologically verified frontotemporal dementia (FTD) due to the intronic tau exon 10(+16) mutation.
  65. pmc Tau isoform composition influences rate and extent of filament formation
    Qi Zhong
    Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 287:20711-9. 2012
    ..tauopathic neurodegenerative disease depends in part on the levels and composition of six naturally occurring Tau isoforms in human brain...
  66. pmc Fibrillization of human tau is accelerated by exposure to lead via interaction with His-330 and His-362
    Hai Li Zhu
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China
    PLoS ONE 6:e25020. 2011
    Neurofibrillary tangles, mainly consisted of bundles of filaments formed by the microtubule-associated protein Tau, are a hallmark of Alzheimer disease...
  67. ncbi Tau negative frontal lobe dementia at 17q21: significant finemapping of the candidate region to a 4.8 cM interval
    R Rademakers
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp UIA, Antwerpen, Belgium
    Mol Psychiatry 7:1064-74. 2002
    ..In addition we excluded mutations in the prion protein gene and exons 9-13 of the microtubule associated protein tau (MAPT) gene...
  68. ncbi Triggers of full-length tau aggregation: a role for partially folded intermediates
    Carmen N Chirita
    Biophysics Program, The Ohio State University, Columbus, Ohio 43210, USA
    Biochemistry 44:5862-72. 2005
    Alzheimer's disease is characterized in part by the accumulation of full-length tau proteins into intracellular filamentous inclusions...
  69. ncbi CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival
    Hideki Shimura
    Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 279:4869-76. 2004
    The microtubule-binding protein tau has been implicated in the neurofibrillary pathology of Alzheimer's disease. Within affected cells, ubiquitinated and hyperphosphorylated tau assembles into massive filamentous polymers...
  70. pmc Evaluation of microtubule-associated protein-Tau expression as a prognostic and predictive marker in the NSABP-B 28 randomized clinical trial
    Lajos Pusztai
    Department of Breast Medical Oncology, The University of Texas M D Anderson Cancer Center, PO Box 301439, Houston, TX 77230 1439, USA
    J Clin Oncol 27:4287-92. 2009
    We assessed Tau protein expression in primary breast cancer specimens of patients included in the National Surgical Breast and Bowel Project (NSABP) -B 28 clinical trial...
  71. ncbi Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17
    M Hong
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 282:1914-7. 1998
    b>Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegenerative diseases, including Alzheimer's disease and hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)...
  72. ncbi Global hairpin folding of tau in solution
    Sadasivam Jeganathan
    Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, D 22607 Hamburg, Germany
    Biochemistry 45:2283-93. 2006
    The microtubule-associated protein tau stabilizes microtubules in its physiological role, whereas it forms insoluble aggregates (paired helical filaments) in Alzheimer's disease...
  73. doi Phosphorylation of soluble tau differs in Pick's disease and Alzheimer's disease brains
    Janet van Eersel
    Discipline of Pathology, The University of Sydney, Sydney, NSW, 2006, Australia
    J Neural Transm (Vienna) 116:1243-51. 2009
    ..disease (PiD) is a subtype of FTLD, which presents with intraneuronal inclusions consisting of hyperphosphorylated tau protein aggregates...
  74. pmc Familial FTDP-17 missense mutations inhibit microtubule assembly-promoting activity of tau by increasing phosphorylation at Ser202 in vitro
    Dong Han
    Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital
    J Biol Chem 284:13422-33. 2009
    ..disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and other tauopathies, tau accumulates and forms paired helical filaments (PHFs) in the brain...
  75. pmc A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration
    Kanae Iijima-Ando
    Laboratory of Neurogenetics and Pathobiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Hum Mol Genet 19:1930-8. 2010
    Hyperphosphorylation of the microtubule associated protein tau is detected in the brains of individuals with a range of neurodegenerative diseases including Alzheimer's disease (AD)...
  76. ncbi NMR investigation of the interaction between the neuronal protein tau and the microtubules
    Alain Sillen
    CNRS UMR 8576 Unité de Glycobiologie Structurale et Fonctionnelle, Université des Sciences et Technologies de Lille 1, 59655, Villeneuve d Ascq Cedex, France
    Biochemistry 46:3055-64. 2007
    Whereas the interaction between Tau and the microtubules has been studied in great detail both by macroscopic techniques (cosedimentation, cryo-electron microscopy, and fluorescence spectroscopy) using the full-length protein or by ..
  77. ncbi Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation
    Q Zheng-Fischhöfer
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    Eur J Biochem 252:542-52. 1998
    AT100 is a monoclonal antibody highly specific for phosphorylated Tau in Alzheimer paired helical filaments...
  78. pmc Co-localization of amyloid beta and tau pathology in Alzheimer's disease synaptosomes
    Jeffrey A Fein
    School of Nursing, University of California at Los Angeles School of Medicine, Sepulveda Veterans Administration Medical Center, Los Angeles, California 90095 6919, USA
    Am J Pathol 172:1683-92. 2008
    The amyloid cascade hypothesis proposes that amyloid beta (Abeta) pathology precedes and induces tau pathology, but the neuropathological connection between these two lesions has not been demonstrated...
  79. ncbi A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia
    Roneil Malkani
    Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, 35, Convent Drive, Bethesda, MD 20892, USA
    Neurobiol Dis 22:401-3. 2006
    ..This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease...
  80. pmc Alzheimer's disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits
    Katharina Schindowski
    INSERM U815, Place de Verdun, 59045 Lille Cedex, France
    Am J Pathol 169:599-616. 2006
    b>Tau transgenic mice are valuable models to investigate the role of tau protein in Alzheimer's disease and other tauopathies...
  81. pmc Phosphorylated Tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer disease
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney, Camperdown, New South Wales 2050, Australia
    J Biol Chem 284:20909-16. 2009
    In Alzheimer disease (AD) and frontotemporal dementia the microtubule-associated protein Tau becomes progressively hyperphosphorylated, eventually forming aggregates...
  82. pmc The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's disease
    Amy Gerrish
    MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
    J Alzheimers Dis 28:377-87. 2012
    ..However, the gene-wide effect observed at MAPT indicates a possible contribution to disease risk which requires further study...
  83. pmc Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
    Virginia M Y Lee
    Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cold Spring Harb Perspect Med 1:a006437. 2011
    ..presence of inclusions within neurons that are comprised of fibrils formed from the microtubule-stabilizing protein tau. The formation of misfolded multimeric tau species is believed to contribute to the progressive neuron loss and ..
  84. ncbi The tau H2 haplotype is almost exclusively Caucasian in origin
    Whitney Evans
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Neurosci Lett 369:183-5. 2004
    We have assessed the distribution of the tau H1/H2 haplotype in the publicly available reference series of samples with representatives of most racial groups...
  85. doi Brain perfusion patterns in familial frontotemporal lobar degeneration
    H Seelaar
    Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
    Neurology 77:384-92. 2011
    ..The aim of this study was to compare clinical features and perfusion patterns on SPECT of patients with familial FTLD-TAR DNA binding protein 43 kDa (TDP) and MAPT mutations...
  86. ncbi Association of the tau haplotype H2 with age at onset and functional alterations of glucose utilization in frontotemporal dementia
    Simon M Laws
    Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Munich University of Technology, 81675 Munich, Germany
    Am J Psychiatry 164:1577-84. 2007
    The microtubule-associated protein tau gene (MAPT) contains two extended haplotypes, H1 and H2, which have been linked with sporadic tauopathies...
  87. pmc Pathogenic missense MAPT mutations differentially modulate tau aggregation propensity at nucleation and extension steps
    Edward Chang
    Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA
    J Neurochem 107:1113-23. 2008
    Mutations in the MAPT gene encoding tau protein lead to neurofibrillary lesion formation, neurodegeneration, and cognitive decline associated with frontotemporal lobar degeneration...
  88. doi 5'-Upstream variants of CRHR1 and MAPT genes associated with age at onset in progressive supranuclear palsy and cortical basal degeneration
    Carlos Cruchaga
    Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Pamplona, Spain
    Neurobiol Dis 33:164-70. 2009
    ..Its location at 160 kb and 50 kb upstream of tau and CRHR1 genes, respectively, suggests that it might act as a cis-element that regulates gene expression...
  89. ncbi Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia
    P Poorkaj
    Department of Medicine, University of Washington, Seattle, WA 98108, USA
    Arch Neurol 58:383-7. 2001
    Mutations in the tau gene have been reported in families with frontotemporal dementia (FTD) linked to chromosome 17...
  90. ncbi A minimal length between tau exon 10 and 11 is required for correct splicing of exon 10
    Qingming Yu
    Department of Medicine and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Neurochem 90:164-72. 2004
    Mutations that stimulate exon 10 inclusion into the human tau mRNA cause frontotemporal dementia with parkinsonism, associated with chromosome 17 (FTDP-17), and other tauopathies...
  91. ncbi Novel haplotypes in 17q21 are associated with progressive supranuclear palsy
    Pau Pastor
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 56:249-58. 2004
    ..sporadic neurodegenerative diseases presenting as atypical parkinsonian disorders, characterized by the presence of tau-positive neurofibrillary tangles. Recently, an extended haplotype (H1E) of 787...
  92. ncbi Tau phosphorylation in Alzheimer's disease: pathogen or protector?
    Hyoung gon Lee
    Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106 USA
    Trends Mol Med 11:164-9. 2005
    ..As such, in Alzheimer's disease, phosphorylated tau protein, the major component of neurofibrillary tangles, is considered a central mediator of disease pathogenesis...
  93. ncbi Quantitative analysis of tau isoform transcripts in sporadic tauopathies
    J W Connell
    Department of Neuroscience, Institute of Psychiatry, King s College London, De Crespigny Park, London SE5 8AF, UK
    Brain Res Mol Brain Res 137:104-9. 2005
    ..diseases, including Alzheimer's disease (AD), are characterized by intraneuronal accumulation of the tau protein. Some forms of FTDP-17 are caused by mutations in the tau gene affecting exon 10 splicing...
  94. ncbi Fine mapping of the MAPT locus using quantitative trait analysis identifies possible causal variants in Alzheimer's disease
    S M Laws
    Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technische Universitat Munchen, Munchen, Germany
    Mol Psychiatry 12:510-7. 2007
    ..of Alzheimer's disease (AD) pathology, suggesting a clear involvement of the microtubule-associated protein tau (MAPT) in AD...
  95. doi Exploring gene-environment interactions in Parkinson's disease
    Colin C McCulloch
    Applied Statistics Laboratory, General Electric Global Research Center, Niskayuna, NY, USA
    Hum Genet 123:257-65. 2008
    ..disease (PD) risk; namely, alpha-synuclein (SNCA) promoter polymorphism REP1, microtubule-associated protein tau (MAPT) H1/H2 haplotypes, apolipoprotein E (APOE) epsilon2/epsilon3/epsilon4 polymorphism, ubiquitin carboxy-..
  96. pmc A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series
    Jonathan Beck
    MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Brain 131:706-20. 2008
    ..in the progranulin gene (GRN) are a major cause of frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) but the distinguishing clinical and anatomical features of this subgroup remain ..
  97. pmc Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 8:393-9. 1989
    We have isolated cDNA clones encoding a 383-amino acid isoform of the human microtubule-associated protein tau. It differs from previously determined tau sequences by the presence of an additional repeat of 31 amino acids, giving four, ..
  98. ncbi Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase p110mark. Phosphorylation sites and regulation of microtubule dynamics
    S Illenberger
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    J Biol Chem 271:10834-43. 1996
    ..kinase, termed p110 microtubule-affinity regulating kinase ("MARK"), phosphorylates microtubule-associated protein tau at the KXGS motifs in the region of internal repeats and causes the detachment of tau from microtubules (Drewes, G...
  99. ncbi Tau is enriched on dynamic microtubules in the distal region of growing axons
    M M Black
    Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Neurosci 16:3601-19. 1996
    It is widely held that tau determines the stability of microtubules in growing axons, although direct evidence supporting this hypothesis is lacking...
  100. ncbi Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 409:57-62. 1997
    ..neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated microtubule-associated protein tau. Many of the hyperphosphorylated sites in tau are serine/threonine-prolines...
  101. ncbi Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits
    J R Murrell
    Department of Pathology and Laboratory Medicine and Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis 46202, USA
    J Neuropathol Exp Neurol 58:1207-26. 1999
    Exonic and intronic mutations in Tau cause familial neurodegenerative syndromes characterized by frontotemporal dementia and dysfunction of multiple cortical and subcortical circuits. Here we describe a G389R mutation in exon 13 of Tau...

Research Grants84

  1. Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors for
    ALAN D SNOW; Fiscal Year: 2011
    ..disease (AD) is characterized by brain amyloid plaques consisting of insoluble beta-amyloid (A2) and tau protein containing neurofibrillary tangles (NFTs)...
  2. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
    ..as 'senile'[unreadable]-amyloid plaques, neurofibrillary tangles comprised of abnormally phosphorylated tau protein, and neuronal dysfunction and loss...
  3. Marc I Diamond; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Cell-cell transfer and propagation of tau aggregates. Tauopathies are devastating neurodegenerative diseases...
  4. Canonical Wnt Signaling by the Proteolytc Processing of LRP6
    BRANDON RICHARD BEAGLE; Fiscal Year: 2010
    ..over 40 different proteins and has been implicated in generating aberrantly hyperphosporylated tau proteins associated with AD and other tauopathies...
  5. Gloria Lee; Fiscal Year: 2016
    ..One of the neuropathological features of AD is the neurofibrillary tangles made of abnormally phosphorylated tau protein...
  6. Genomic Analysis of Alzheimer's Disease Genes
    GERARD DAVID SCHELLENBERG; Fiscal Year: 2013
    Abnormally aggregates of the protein tau in the form of neurofibrillary tangles (NFT's) and glial tangles are found in a number of neurodegenerative diseases including Alzheimer's disease (AD) and frontotemporal dementia with ..
  7. Carlos Cruchaga; Fiscal Year: 2016
    ..Novel protein biomarkers for Alzheimer's disease in cerebrospinal fluid;(Richard Perrin) 2. Changing tau protein levels and tau protein isoforms in mouse models of dementia;(Timothy Miller) 3...
  8. David Morgan; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): Tau pathology is implicated as a pathogenic factor in a number of neurodegenerative disorders...
  9. Hillel Grossman; Fiscal Year: 2014
    ..The two defining neuropatholic features of AD are abnormal aggregation and deposition of A2 peptides and tau in the brain as, respectively, extracellular neuritic plaques (NP) and intracellular neurofrillary tangles (NFT)...
  10. A Model of Early Alzheimer Disease
    Bradley T Hyman; Fiscal Year: 2012
    ..We have established a transgenic model in which P301L tau overexpression is limited to the same set of stellate neurons most vulnerable for tangle formation in AD, layer II ..
  11. TRUMAN C GAMBLIN; Fiscal Year: 2015
    ..and is characterized pathologically by the intraneuronal deposition of abnormally phosphorylated and aggregated tau protein and by the formation of extracellular amyloid plaques...
  12. Hyperphosphorylated tau as drug target
    Min Hao Kuo; Fiscal Year: 2012
    ..AD and several other devastating neurodegenerative disorders are collectively known as tauopathies in which the tau protein becomes pathologically hyperphosphorylated and aggregates into the neurofibrillary tangles (NFT) in neuron ..
  13. Karen E Duff; Fiscal Year: 2015
    ..In general, we hypothesize that the UPS is upregulated to clear misfolded tau species early during the disease, but the system becomes overwhelmed as larger aggregates of tau accumulate...
  14. Chad A Dickey; Fiscal Year: 2016
    ..by applicant): The Hsp90-associated enzyme-FK506 binding protein 51 (FKBP51)-was recently found to co-localize with tau in neurons and physically interact with the microtubule (MT)-associated protein tau in brain tissue from humans who ..
  15. Brian C Kraemer; Fiscal Year: 2016
    ..We have previously reported a C. elegans model for the tau pathology seen in human tauopathy disorders including and AD...
  16. In vivo neurophysiological study of a neurodegenerative mouse model
    Daoyun Ji; Fiscal Year: 2013
    ABSTRACT A hallmark of Alzheimer's disease is the progressive appearance of hyper-phosphorylated tau protein, tau neurofibrillary tangles, and neuron loss in the memory-processing circuits including the hippocampus...
  17. Mel B Feany; Fiscal Year: 2016
    ..and is characterized pathologically by the intraneuronal deposition of abnormally phosphorylated and aggregated tau protein and by the formation of extracellular amyloid plaques...
  18. Generation of a Transgenic Mouse Model for Functional Study of a Novel Gene FG01
    Huaxi Xu; Fiscal Year: 2010
    ..neurofibrillary tangles (NFTs) composed of hyperphosphorylated twisted filaments of the microtubule-associated tau protein are two major pathological hallmarks of AD...
  19. Mahalia S Desruisseaux; Fiscal Year: 2015
    ..We demonstrated that tau, a protein involved in neurofibrillary tangle formation in Alzheimer's disease, is aberrantly phosphorylated ..
  20. NASSER HUSSEIN ZAWIA; Fiscal Year: 2014
    ..in Alzheimer's disease (AD) are the extracellular amyloid beta (A[unreadable]) plaques and intracellular tau tangles...
  21. Pharmacological modulation of tau neurotoxicity in vivo
    Mel B Feany; Fiscal Year: 2012
    ..Alzheimer's disease and related disorders, we have created models of the disorder based on expression of human tau and Abeta in the fruit fly Drosophila. Our models recapitulate key features of the human disorders...
  22. Novel PET imaging agents for early diagnosis of plaque deposition in Alzheimer's
    Padmakar Kulkarni; Fiscal Year: 2010
    ..Amyloid is the dangerous brain plaque and tau protein tangles with in the brain cells tend to prevent neurons from communicating each other leading to loss of ..
  23. Brian C Kraemer; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Lesions containing abnormal aggregated tau protein are one of the diagnostic hallmarks of Alzheimer's disease (AD) and related tauopathy disorders...
  24. TDP-43 acetylation as a pathogenic modification in ALS &related proteinopathies
    TODD JONATHAN COHEN; Fiscal Year: 2013
    ..Using my background in acetylation biology, I previously demonstrated that acetylation of the tau protein promotes tangle formation in Alzheimer's disease and related tauopathies (Nat Commun. 2011~2:252)...
  25. Autoimmune biomarker profiling in tauopathy
    Irving E Vega; Fiscal Year: 2013
    ..intracellular aggregation of filaments predominantly composed of hyperphosphorylated microtubule-associated protein tau. This family of neurodegenerative disorders includes Alzheimer's disease, corticobasal degeneration, ..
  26. The role of a novel tau-associated protein in neurodegeneration
    Irving E Vega; Fiscal Year: 2012
    ..by the intracellular aggregation of filaments derived from hyperphosphorylated microtubule-associated protein tau. This family of neurodegenerative disorders includes Alzheimer's disease, corticobasal degeneration, ..
  27. JADA M LEWIS; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): The tau protein plays a fundamental role in the cytoarchitecture of the brain and in axonal transport;however, its function and regulation can be disrupted as it becomes hyperphosphorylated and ..
  28. Robert A Whittington; Fiscal Year: 2016
    ..Intraneuronal neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein, are one of the main neuropathological hallmarks of AD, and anesthetics have been previously demonstrated ..
  29. DAVID WINLAND SANDERS; Fiscal Year: 2014
    ..heterogeneous group of neurodegenerative diseases, feature insoluble deposits of the microtubule-associated protein tau. A causal role for tau misfolding in disease is supported by the fact that multiple mutations associated with an ..
  30. Alzhelmer's Disease Drug Development Program
    Amos B Smith; Fiscal Year: 2012
    ..Central to this hypothesis is the understanding that the MT-stabilizing tau proteins of the central nervous system (CMS) are sequestered into filamentous inclusions that are the signature ..
  31. Giulio Taglialatela; Fiscal Year: 2016
    ..of amyloid beta (A[unreadable]) plaques and the presence of neurofibrillary tangles of hyper-phosphorylated tau protein are the two CNS lesions that, concomitant with synaptic disruption and preponderant insulin resistance, ..
  32. Delineating conformational variants of the Abeta peptide
    Joel Watts; Fiscal Year: 2013
    ..of amyloid plaques containing A[unreadable] peptide as well as neurofibrillary tangles (NFTs) harboring aggregated tau protein in the central nervous system...
  33. Neuroimaging Biomarkers in Mouse Models of AD
    Robia G Pautler; Fiscal Year: 2012
    ..activated glial cells as well as intracellular neurofibrillary tangles that are comprised of hyperphosphorylated tau protein aggregates...
  34. Qubai Hu; Fiscal Year: 2014
    ..plaques consisting of insoluble beta-amyloid protein (A?), and neurofibrillary tangles (NFTs) containing aggregated tau protein...
  35. Novel Stem Cell and Mouse Models to Study Frontotemporal Dementia
    MIRANDA ETHEL ORR; Fiscal Year: 2010
    ..Mice with mutations in the microtubule associated protein tau gene accurately model biochemical, histological, and behavioral aspects of human FTD...
  36. A Diarylheptanoid Scaffold to Treat Taopathies
    Chad A Dickey; Fiscal Year: 2013
    ..Myrica cerifera (Southern Bayberry) extract using a systematic screen as a potent reducer of the structural protein tau, which accumulates in a group of diseases called the "tauopathies"...
  37. JOEL SYNES PERLMUTTER; Fiscal Year: 2016
    ..pathology or co-existing Alzheimer's (AD) pathology that includes abnormal deposition of A[unreadable] and tau proteins. Our recent studies suggest that this may be an oversimplification...
  38. Targeting Tau Splicing for Dementia
    Michael S Wolfe; Fiscal Year: 2013
    ..provided by applicant): The amyloid-[unreadable] peptide (A[unreadable]) and the microtubule-associated protein tau are both strongly implicated in the pathogenesis of Alzheimer's disease (AD)...
  39. GARY ALLEN ROSENBERG; Fiscal Year: 2016
    ..This aim is focused on determining the implications of amyloid and tau proteins in the CSF of SIVD patients...
  40. Bradley T Hyman; Fiscal Year: 2014
    ..They consist of hyperphosphorylated tau that aggregates in the neuronal cell body. Cross sectional histological studies suggest that tangles kill neurons...
  41. Tau polymerization as a target for Alzheimer's disease
    TRUMAN C GAMBLIN; Fiscal Year: 2010
    ..I plan to reach this objective by studying the changes in the microtubule-associated protein tau that lead to a decrease in its normal functions and increase its pathological ability to self-assemble into ..
  42. Changing tau Protein Levels and tau Protein Isoforms in Mouse Models of Dementia
    Timothy M Miller; Fiscal Year: 2012
    ..Miller is now using a similar strategy to either decrease overall levels of tau or decrease the 4R:3R tau ratio by changing exon splicing...
  43. Conrad C Weihl; Fiscal Year: 2016
    ..These structures contain ubiquitinated and undegraded insoluble proteins that include ss-amyloid and phosphorylated tau; proteins that accumulate in Alzheimer's Disease brains...
  44. Brian A Warmus; Fiscal Year: 2015
    ..b>Tau mutations cause FTD, and we have found several FTD-relevant behavioral abnormalities in a transgenic mouse ..
  45. Novel Hsp90 Inhibitors to Reduce Misfolded Proteins in Alzheimer's Disease
    Mary L Michaelis; Fiscal Year: 2011
    ..Activation or up-regulation of these chaperone complexes reduces amyloid peptide (Ap) aggregates and fibrillar Tau protein in transgenic mouse models of AD neuropathology. However, most known Hsp90 inhibitors are quite toxic...
  46. Tau in cancer cells
    Gloria Lee; Fiscal Year: 2010
    ..many age-related neurodegenerative diseases, neuronal loss is correlated with the presence of hyperphosphorylated tau. In Alzheimer's disease, it has been hypothesized that neurons die because cell cycle mechanisms have been ..
  47. BRANDON BLAKE HOLMES; Fiscal Year: 2014
    ..of neurodegenerative disorders characterized by the pathological accumulation of microtubule-associated protein tau in the human brain...
  48. O-GlcNAcylation of tau: a link between glucose metabolism and neurodegeneration
    Cheng Xin Gong; Fiscal Year: 2010
    Abnormal hyperphosphorylation and aggregation of tau protein in the brain are critical to neurodegeneration of Alzheimer diesease (AD). Glucose uptake/metabolism is impaired in AD brain, which is believed to cause neurodegeneration...
  49. Chaperone-mediated signaling in Alzheimer's disease
    Chad A Dickey; Fiscal Year: 2010
    ..of Alzheimer's disease (AD) is the formation of neurofibrillary tangles (NFT) composed of hyper-phosphorylated tau (p-tau), a process closely linked to neurodegeneration...
  50. MICHELE LAURA LENOUE-NEWTON; Fiscal Year: 2014
    ..Neurofibrillary tangles are composed of hyperphosphorylated tau protein (5, 6). Normal tau is a microtubule-associated protein that stabilizes microtubules (7)...
  51. AGING AND ALZHEIMER DEMENTIA--ROLE OF FIBROUS PROTEINS
    Shu Hui Yen; Fiscal Year: 2000
    ..helical filaments and biochemically similar 15-18 nm diameter straight filaments are composed of microtubule associated protein tau. Biochemical studies have shown that some PHF are soluble in sodium dodecyl sulfate (SDS) while ..
  52. Scott K Silverman; Fiscal Year: 2016
    ..deoxyribozymes in biologically relevant contexts such as cell-surface modification reactions and studies of tau protein, which is implicated in Alzheimer's disease...
  53. Alzheimer's Disease Cooperative Study (ADCS)
    Paul S Aisen; Fiscal Year: 2012
    ..biological signal for consideration for future efficacy trials: (1) Li, a molecule that blocks phosphorylation of tau protein and (2) resveratrol, a polyphenol derived from plants and red wine that retards the age-dependent ..
  54. William M Valentine; Fiscal Year: 2014
    ..modifications by shotgun LC/MS/MS, map neurodegenerative changes and quantify the expression and phosphorylation of tau and -synuclein...
  55. Extracellular Zinc Buffering and A-beta Oligomerization
    GUIDO FAAS; Fiscal Year: 2012
    ..of AD are not well understood it is known that AD is a proteopathy leading to intracellular accumulation of tau protein and extracellular amyloid 2 (Ab) aggregates (senile plaques)...
  56. Einar M Sigurdsson; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Harnessing the immune system to target pathological tau protein has recently become attractive as a potential therapy for Alzheimer's disease (AD) and related tauopathies...
  57. Jason Chen; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): The role of the tau protein in neurological diseases is an important open question, given that it has been demonstrated as a central driver of neurodegeneration...
  58. IN VIVO ANALYSIS OF RATIONALLY IDENTIFIED INHIBITOR OF AMYLOID B_PROTEIN ASSEMBLY
    AIDA ATTAR; Fiscal Year: 2012
    ..compound as an inhibitor of the self-assembly and neurotoxicity of amyloid 2-protein (A2) and potentially the tau protein - the main proteins believed to cause Alzheimer's disease (AD)...
  59. ASHLEY LINDA KEES; Fiscal Year: 2014
    ..Connectivity between the two regions has been implicated in both Alzheimer's and schizophrenia: the tau protein that causes Alzheimer's spreads across synapses, and errant connectivity might be responsible for a ..
  60. Prolyl Isomerase Pin 1 and Neurodegeneration
    Kun Ping Lu; Fiscal Year: 2009
    ..disease (AD) and related disorders is the neurofibrillary tangles, whose main component is hyperphosphorylated tau, a microtubule-binding protein...
  61. Hui Zheng; Fiscal Year: 2016
    ..components are A[unreadable] peptides derived from the amyloid precursor protein (APP) and hyper-phosphorylated tau, respectively...
  62. Probing early protein aggregation mechanisms and their relationship to disease ef
    SongI Han; Fiscal Year: 2011
    ..I will focus in the first years on the study of tau whose fibrous tangles are found in Alzheimer's and other neurodegenerative diseases...
  63. Structure-based Ligand Design of Inhibitors that Prevent Tau Aggregation
    Collin M Stultz; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Tau is a natively unfolded protein that has been implicated in the pathogenesis of several neurodegenerative disorders such as Alzheimer's disease (AD)...
  64. Tau Nitration and Oxidation in Alzheimer's Disease
    LESTER IRVIN BINDER; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Tau proteins normally stabilize microtubules in neuronal processes in the brain...
  65. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Filamentous deposits of hyperphosphorylated tau proteins are a major pathological hallmark of a large number of dementing disorders, such as Alzheimer's disease (AD) and frontotemporal dementia ..
  66. Mechanisms of Tau-Based Neurodegeneration
    Mark Forman; Fiscal Year: 2005
    Filamentous tau inclusions in neurons, astrocytes and oligodendrocytes are the neuropathological hallmark of both sporadic and familial tauopathies...
  67. Understanding/ Treating Neuropsychiatric Symptoms of Pediatric Physical Illness
    Eva Szigethy; Fiscal Year: 2009
    ..abstract_text> ..
  68. Structure and Function of Tau Protein
    Stuart C Feinstein; Fiscal Year: 2010
    The microtubule associated protein tau is essential for the development and maintenance of the nervous system...
  69. A cell base system for compounds regulating tau splicing
    Jianhua Zhou; Fiscal Year: 2004
    Tauopathies, formation of insoluble intraneuronal aggregates made of tau protein are major clinical features of several neurodegenerative disorders including frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17)...
  70. PATHOBIOLOGY OF TAU PROTEIN
    KENNETH KOSIK; Fiscal Year: 1999
    ..Kinases and phosphatases that interact with the projection domain of MAP2 and tau will be identified and the interaction characterized...
  71. PHOSPHORYLATION AND SPATIAL LOCALIZATION OF TAU PROTEIN
    Gloria Lee; Fiscal Year: 2004
    b>Tau is a microtubule-associated protein that is the primary component of neurofibrillary tangles in Alzheimer's disease...
  72. STRUCTURE AND FUNCTION OF MOUSE TAU PROTEIN
    Gloria Lee; Fiscal Year: 1992
    ..The goal of this proposal is to investigate the structure, function and expression of tau protein, a microtubule associated protein whose properties suggest that it might determine microtubule organization ..
  73. Chaperone-mediated signaling in Alzheimer's disease
    Chad Dickey; Fiscal Year: 2007
    ..of Alzheimer's disease (AD) is the formation of neurofibrillary tangles (NFT) composed of hyper-phosphorylated tau (p-tau), a process closely linked to neurodegeneration...
  74. High throughput tau oligomer assay for drug screening for Alzheimer's disease
    James Moe; Fiscal Year: 2007
    ..These insoluble protein deposits are composed of either tau protein associated with neurofibrillary tangles (NFTs), or [unreadable]-amyloid (A-[unreadable]) protein associated ..
  75. Modeling of Mouse and Human Tau Interactions
    Stephanie Adams; Fiscal Year: 2009
    ..pathology in AD and other neurodegenerative diseases results from the aggregation and deposition of normal tau proteins...