tau proteins

Summary

Summary: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).

Top Publications

  1. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
  2. ncbi Alzheimer's disease
    Kaj Blennow
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren s University Hospital, Molndal, Sweden
    Lancet 368:387-403. 2006
  3. pmc The many faces of tau
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 70:410-26. 2011
  4. pmc Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
    Clifford R Jack
    Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA jack cliff
    Lancet Neurol 9:119-28. 2010
  5. pmc Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
    Leslie M Shaw
    Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann Neurol 65:403-13. 2009
  6. 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
  7. ncbi A century of Alzheimer's disease
    Michel Goedert
    Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, UK
    Science 314:777-81. 2006
  8. pmc Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration
    Nigel J Cairns
    Department of Neurology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St Louis, MO, 63110, USA
    Acta Neuropathol 114:5-22. 2007
  9. pmc Caspase activation precedes and leads to tangles
    Alix de Calignon
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 464:1201-4. 2010
  10. doi CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment
    Niklas Mattsson
    Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, the Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden
    JAMA 302:385-93. 2009

Detail Information

Publications405 found, 100 shown here

  1. ncbi The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics
    John Hardy
    Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
    Science 297:353-6. 2002
    ..The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Abeta production and Abeta clearance...
  2. ncbi Alzheimer's disease
    Kaj Blennow
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren s University Hospital, Molndal, Sweden
    Lancet 368:387-403. 2006
    ..This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies...
  3. pmc The many faces of tau
    Meaghan Morris
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 70:410-26. 2011
    ..In this review, we highlight these functions and the potential roles of tau in neurodegenerative disease. We also discuss the therapeutic potential of drugs targeting various aspects of tau biology...
  4. pmc Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
    Clifford R Jack
    Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA jack cliff
    Lancet Neurol 9:119-28. 2010
    ....
  5. pmc Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
    Leslie M Shaw
    Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann Neurol 65:403-13. 2009
    ..Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects...
  6. 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
    ..Our findings suggest that this dendritic role of tau confers Abeta toxicity at the postsynapse with direct implications for pathogenesis and treatment of AD...
  7. ncbi A century of Alzheimer's disease
    Michel Goedert
    Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, UK
    Science 314:777-81. 2006
    ..Genetic studies have shown that dysfunction of amyloid-beta or tau is sufficient to cause dementia. The ongoing molecular dissection of the neurodegenerative pathways is expected to lead to a true understanding of disease pathogenesis...
  8. pmc Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration
    Nigel J Cairns
    Department of Neurology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St Louis, MO, 63110, USA
    Acta Neuropathol 114:5-22. 2007
    ..These criteria will be of value to the practicing neuropathologist and provide a foundation for clinical, clinico-pathologic, mechanistic studies and in vivo models of pathogenesis of FTLD...
  9. pmc Caspase activation precedes and leads to tangles
    Alix de Calignon
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nature 464:1201-4. 2010
    ..Because tangle-bearing neurons are long-lived, we suggest that tangles are 'off pathway' to acute neuronal death. Soluble tau species, rather than fibrillar tau, may be the critical toxic moiety underlying neurodegeneration...
  10. doi CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment
    Niklas Mattsson
    Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, the Sahlgrenska Academy at University of Gothenburg, Molndal, Sweden
    JAMA 302:385-93. 2009
    ....
  11. pmc Propagation of tau pathology in a model of early Alzheimer's disease
    Alix de Calignon
    MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Neuron 73:685-97. 2012
    ..These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process ..
  12. pmc Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease
    Erik D Roberson
    Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA
    J Neurosci 31:700-11. 2011
    ..Our results indicate that Aβ, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit...
  13. ncbi Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils
    J Gotz
    Division of Psychiatry Research, University of Zurich, August Forel Strasse 1, 8008 Zurich, Switzerland
    Science 293:1491-5. 2001
    ..NFTs were composed of twisted filaments and occurred in 6-month-old mice as early as 18 days after Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can accelerate NFT formation in vivo...
  14. 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
    ..In general, the mouse recapitulates the tauopathy that defines the early stages of AD and provides a model for testing mechanisms and functional outcomes associated with disease progression...
  15. pmc Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration
    Ming Jin
    Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:5819-24. 2011
    ..Insoluble fibrillar plaques of amyloid β-proteins (Aβ) and neurofibrillary deposits of hyperphosphorylated tau proteins are the diagnostic lesions of AD, but their temporal mechanistic relationship has long been debated...
  16. ncbi Tau-mediated neurodegeneration in Alzheimer's disease and related disorders
    Carlo Ballatore
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104 4283, USA
    Nat Rev Neurosci 8:663-72. 2007
    ....
  17. pmc Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease
    Gunnar K Gouras
    Department for Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA
    Acta Neuropathol 119:523-41. 2010
    ....
  18. doi Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease
    Lars M Ittner
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, The University of Sydney, Camperdown, 100 Mallett Street, NSW 2050, Australia
    Nat Rev Neurosci 12:65-72. 2011
    ..As we gain a deeper understanding of the different cellular functions of tau, the focus shifts from the axon, where tau has a principal role as a microtubule-associated protein, to the dendrite, where it mediates amyloid-β toxicity...
  19. 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
    ..Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease...
  20. pmc Transmission and spreading of tauopathy in transgenic mouse brain
    Florence Clavaguera
    Department of Neuropathology, Institute of Pathology, University of Basel, Switzerland
    Nat Cell Biol 11:909-13. 2009
    ....
  21. pmc Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments
    A Alonso
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    Proc Natl Acad Sci U S A 98:6923-8. 2001
    ....
  22. pmc Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy
    Günter U Höglinger
    Department of Neurology, Philipps Universitat, Marburg, Germany
    Nat Genet 43:699-705. 2011
    ..The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component...
  23. ncbi Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
    Oskar Hansson
    Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund University, Sweden
    Lancet Neurol 5:228-34. 2006
    ..Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI)...
  24. pmc Neuropathological background of phenotypical variability in frontotemporal dementia
    Keith A Josephs
    Behavioral Neurology and Movement Disorders, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
    Acta Neuropathol 122:137-53. 2011
    ..However, there appears to be some associations between clinical phenotypes and FTLD-FUS pathologies. Clinical diagnosis is therefore promising in predicting molecular pathology...
  25. doi Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia
    Peder Buchhave
    Neuropsychiatric Clinic, Skane University Hospital, Malmo, Sweden
    Arch Gen Psychiatry 69:98-106. 2012
    ..Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease...
  26. pmc Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases
    Giovanni Coppola
    Department of Neurology, University of California, Los Angeles, CA, USA
    Hum Mol Genet 21:3500-12. 2012
    ....
  27. pmc Differential regulation of dynein and kinesin motor proteins by tau
    Ram Dixit
    Department of Physiology and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 319:1086-9. 2008
    ..The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport...
  28. pmc Tau is essential to beta -amyloid-induced neurotoxicity
    Mark Rapoport
    Institute for Neuroscience, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 99:6364-9. 2002
    ..peptide (Abeta); neurofibrillary tangles represent intracellular bundles of self-assembled hyperphosphorylated tau proteins. Although these two lesions are often present in the same brain areas, a mechanistic link between them has yet ..
  29. pmc Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice
    J J Lucas
    Centro de Biologia Molecular Severo Ochoa, CSIC Universidad Autonoma de Madrid, Departamento de Morfologia, Facultad de Medicina, Universidad Autonoma de Madrid, 28049 Madrid, Spain
    EMBO J 20:27-39. 2001
    ....
  30. pmc Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases
    Takashi Nonaka
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo 156 8585, USA
    J Biol Chem 285:34885-98. 2010
    ..Our cellular models thus provide evidence of nucleation-dependent and protein-specific polymerization of intracellular amyloid-like proteins in cultured cells...
  31. pmc Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo
    Wendy Noble
    Center for Dementia Research, Nathan S Kline Institute, New York University, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
    Proc Natl Acad Sci U S A 102:6990-5. 2005
    ..These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically...
  32. pmc Tau reduction prevents Abeta-induced defects in axonal transport
    Keith A Vossel
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Science 330:198. 2010
    ..Lowering tau levels prevented these defects without affecting baseline axonal transport. Thus, Aβ requires tau to impair axonal transport, and tau reduction protects against Aβ-induced axonal transport defects...
  33. pmc Propagation of tau misfolding from the outside to the inside of a cell
    Bess Frost
    Department of Neurology, University of California, San Francisco, CA 94143, USA
    J Biol Chem 284:12845-52. 2009
    ..This may have important implications for understanding how protein misfolding spreads through the brains of tauopathy patients, and it is potentially relevant to myriad neurodegenerative diseases associated with protein misfolding...
  34. ncbi Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein
    Bridget Allen
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    J Neurosci 22:9340-51. 2002
    ..No evidence for apoptosis was obtained, despite the extensive colocalization of hyperphosphorylated tau protein with activated MAP kinase family members. The latter may be involved in the hyperphosphorylation of tau...
  35. doi Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years
    Heiko Braak
    Clinical Neuroanatomy, Department of Neurology, and Laboratory for Neuropathology Institute of Pathology, Center for Clinical Research, University of Ulm, Germany
    J Neuropathol Exp Neurol 70:960-9. 2011
    ..0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region...
  36. ncbi CSF markers for incipient Alzheimer's disease
    Kaj Blennow
    Department of Clinical Neuroscience, Sahlgrenska Academy, Gothenburg University, Sweden
    Lancet Neurol 2:605-13. 2003
    ..The CSF biomarkers total tau protein, phosphorylated tau protein, and the 42 amino-acid residue form of amyloid-beta may, if put in the right clinical context, prove to have high enough diagnostic accuracy to meet this challenge...
  37. pmc Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease
    Sudad Saman
    Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA
    J Biol Chem 287:3842-9. 2012
    ..Our results suggest that exosome-mediated secretion of phosphorylated tau may play a significant role in the abnormal processing of tau and in the genesis of elevated CSF tau in early AD...
  38. pmc Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice
    Virginie Rhein
    Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, 4025 Basel, Switzerland
    Proc Natl Acad Sci U S A 106:20057-62. 2009
    ..Our study establishes a molecular link between Abeta and tau protein in AD pathology in vivo, illustrating the potential of quantitative proteomics...
  39. pmc Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration
    Brian R Hoover
    Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
    Neuron 68:1067-81. 2010
    ..Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines...
  40. doi Constitutive secretion of tau protein by an unconventional mechanism
    Xiyun Chai
    Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
    Neurobiol Dis 48:356-66. 2012
    ..If previously postulated pathogenic extracellular tau intermediates are released by this route, low level constitutive tau secretion could play a role in the spread of tau pathology in Alzheimer's disease and other human tauopathies...
  41. pmc Acetylation of tau inhibits its degradation and contributes to tauopathy
    Sang Won Min
    Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
    Neuron 67:953-66. 2010
    ..Inhibiting p300 with a small molecule promoted tau deacetylation and eliminated p-tau associated with tauopathy. Modulating tau acetylation could be a new therapeutic strategy to reduce tau-mediated neurodegeneration...
  42. ncbi Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
    J Lewis
    Birdsall Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Science 293:1487-91. 2001
    ..The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease...
  43. ncbi Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles
    C W Wittmann
    Department of Pathology, Division of Neuropathology, Brigham and Women s Hospital and Harvard Medical School, 221 Longwood Avenue, Room 514, Boston, MA 02115, USA
    Science 293:711-4. 2001
    ..This fly model may allow a genetic analysis of the cellular mechanisms underlying tau neurotoxicity...
  44. pmc Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
    Yipeng Wang
    Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany
    Hum Mol Genet 18:4153-70. 2009
    ....
  45. pdf Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry
    Heiko Braak
    Institute for Clinical Neuroanatomy, J W Goethe University Clinic, Theodor Stern Kai 7, 60590 Frankfurt Main, Germany
    Acta Neuropathol 112:389-404. 2006
    ..It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure...
  46. doi Synaptic degeneration in Alzheimer's disease
    Thomas Arendt
    Paul Flechsig Institute of Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
    Acta Neuropathol 118:167-79. 2009
    ..The molecular mechanisms involved in cell cycle activation might, thus, link aberrant synaptic changes to cell death...
  47. doi Tau phosphorylation: the therapeutic challenge for neurodegenerative disease
    Diane P Hanger
    MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
    Trends Mol Med 15:112-9. 2009
    ..Recent evidence suggests that relatively early disease-associated changes in soluble tau proteins, including phosphorylation, are involved in the induction of neuronal death...
  48. doi The propagation of prion-like protein inclusions in neurodegenerative diseases
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Trends Neurosci 33:317-25. 2010
    ....
  49. pmc FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration
    Hazel Urwin
    UCL Institute of Neurology, London, UK
    Acta Neuropathol 120:33-41. 2010
    ..We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated...
  50. pmc Intraneuronal APP, not free Aβ peptides in 3xTg-AD mice: implications for tau versus Aβ-mediated Alzheimer neurodegeneration
    Matthew J Winton
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:7691-9. 2011
    ..Although we cannot corroborate the presence of intraneuronal Aβ peptide in 3xTg-AD mice, our findings warrant further study as to the role of aberrant APP accumulation in this unique model of AD...
  51. pmc Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles
    Jing L Guo
    Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:15317-31. 2011
    ..In summary, our study establishes a cellular system that robustly develops authentic NFT-like Tau aggregates, which provides mechanistic insights into NFT pathogenesis and a potential tool for identifying Tau-based therapeutics...
  52. pmc E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with age-dependent, detrimental motor impairment
    Kristel L Emmer
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:35104-18. 2011
    ..Collectively, these findings provide insights in the mechanisms of formation of these aberrant proteinaceous inclusions and support the notion that α-syn aggregates are involved in the pathogenesis of human diseases...
  53. ncbi PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila
    Isao Nishimura
    Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Cell 116:671-82. 2004
    ..These findings begin to differentiate the effects of various phosphorylation events on tau toxicity and provide potential therapeutic targets...
  54. pmc Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies
    Celeste M Karch
    Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 287:42751-62. 2012
    ..This study demonstrates that cells actively release Tau in the absence of disease or toxicity, and Tau release is modified by changes in the Tau protein that are associated with tauopathies...
  55. ncbi Inability of tau to properly regulate neuronal microtubule dynamics: a loss-of-function mechanism by which tau might mediate neuronal cell death
    Stuart C Feinstein
    Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
    Biochim Biophys Acta 1739:268-79. 2005
    ..An especially attractive aspect of this model is that it readily accommodates both the structural and regulatory classes of FTDP-17 mutations...
  56. pmc The MAP2/Tau family of microtubule-associated proteins
    Leif Dehmelt
    Department of Cell Biology, The Scripps Research Institute and Institute for Childhood and Neglected Diseases, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Genome Biol 6:204. 2005
    ..Various upstream kinases and interacting proteins have been identified that regulate the microtubule-stabilizing activity of MAP2/Tau family proteins...
  57. pmc Hyperphosphorylation and cleavage at D421 enhance tau secretion
    Vanessa Plouffe
    Departement de pathologie et biologie cellulaire, Universite de Montreal, Montreal, Quebec, Canada
    PLoS ONE 7:e36873. 2012
    ..Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF...
  58. doi Alzheimer's pathogenesis: is there neuron-to-neuron propagation?
    Heiko Braak
    Clinical Neuroanatomy Department of Neurology, Center for Clinical Research, University of Ulm, Ulm, Germany
    Acta Neuropathol 121:589-95. 2011
    ....
  59. doi The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort
    Caroline H Williams-Gray
    Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK
    Brain 132:2958-69. 2009
    ..Our work suggests that the dementing process in Parkinson's disease is predictable and related to tau while frontal-executive dysfunction evolves independently with a more dopaminergic basis and better prognosis...
  60. pmc Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
    Veronique Schaeffer
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Brain 135:2169-77. 2012
    ..Our findings provide direct evidence in favour of the degradation of tau aggregates by autophagy. Activation of autophagy may be worth investigating in the context of therapies for human tauopathies...
  61. doi Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles
    Diana Simon
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
    FEBS Lett 586:47-54. 2012
    ..Hence, we propose that tau might be secreted through membrane vesicles as a cellular mechanism to eliminate the excess of tau protein, thereby avoiding its toxicity...
  62. doi Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort
    N S M Schoonenboom
    Departments of Neurology, VU University Medical Center, Alzheimer Center, Amsterdam, The Netherlands
    Neurology 78:47-54. 2012
    ..To determine how amyloid β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia...
  63. pmc Widespread τ and amyloid-β pathology many years after a single traumatic brain injury in humans
    Victoria E Johnson
    Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA
    Brain Pathol 22:142-9. 2012
    ..This suggests that a single TBI induces long-term neuropathological changes akin to those found in neurodegenerative disease...
  64. pmc Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway
    Yuekui Li
    Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Neurosci 23:1605-11. 2003
    ....
  65. pmc Mechanisms of tau-induced neurodegeneration
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA
    Acta Neuropathol 118:53-69. 2009
    ..AD is multifactorial and heterogeneous and involves more than one etiopathogenic mechanism...
  66. pmc Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β
    Justin M Nussbaum
    Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA
    Nature 485:651-5. 2012
    ..Our results raise the possibility that Aβ(3(pE)-42) acts similarly at a primary step in Alzheimer's disease pathogenesis...
  67. doi Tau transgenic mice as models for cerebrospinal fluid tau biomarkers
    Donna M Barten
    Neuroscience Drug Discovery, Bristol Myers Squibb, Wallingford, CT 06492, USA
    J Alzheimers Dis 24:127-41. 2011
    ..Taken together, these assays and mouse models may be used to facilitate a deeper understanding of CSF tau in neurodegenerative disease...
  68. 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
    ..In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia...
  69. doi CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
    T T Seppälä
    Unit of Neurology, Institute of Clinical Medicine, University of Eastern Finland
    Neurology 78:1568-75. 2012
    ....
  70. doi LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3ß
    Chin Hsien Lin
    Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan
    J Neurosci 30:13138-49. 2010
    ..G2019S increases the recruitment of autoactivated Sgg, thus inducing hyperphosphorylation and mislocalization of tau with resultant dendrite degeneration...
  71. pmc Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important?
    Yaroslau Compta
    Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Brain 134:1493-505. 2011
    ..Cortical amyloid-β and age at disease onset seem to determine the rate to dementia...
  72. pmc Age and diagnostic performance of Alzheimer disease CSF biomarkers
    N Mattsson
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry and Psychiatry, the Sahlgrenska Academy at University of Gothenburg, Mo lndal, Sweden
    Neurology 78:468-76. 2012
    ..These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly...
  73. ncbi Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine
    Enrique J Rivera
    Department of Pathology, Rhode Island Hospital and Brown Medical School, Providence, RI 02903, USA
    J Alzheimers Dis 8:247-68. 2005
    ..Together, these data provide further evidence that AD represents a neuro-endocrine disorder that resembles a unique form of diabetes mellitus (? Type 3) and progresses with severity of neurodegeneration...
  74. doi CSF soluble amyloid precursor proteins in the diagnosis of incipient Alzheimer disease
    R Perneczky
    Department of Psychiatry and Psychotherapy, Technische Universitat Munchen, Klinikum rechts der Isar, 81675 Munchen, Germany
    Neurology 77:35-8. 2011
    ..To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI)...
  75. pmc Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress
    K Stamer
    Max Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
    J Cell Biol 156:1051-63. 2002
    ..The data suggests a linkage between tau and APP trafficking, which may be significant in Alzheimer's disease...
  76. ncbi Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome
    Salvatore Oddo
    Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA 92697, USA
    Neuron 43:321-32. 2004
    ..These findings indicate that Abeta immunization may be useful for clearing both hallmark lesions of AD, provided that intervention occurs early in the disease course...
  77. pmc APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging
    John C Morris
    Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO 63108, USA
    Ann Neurol 67:122-31. 2010
    ..To examine interactions of apolipoprotein E (APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging...
  78. doi Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer's disease
    James Folwell
    Department of Neurosciences, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK
    Exp Neurol 223:401-9. 2010
    ..It is therefore possible to speculate that the mechanism by which Abeta(42) interacts with tau in the pathogenesis of AD is by down-regulating endogenous wnt signalling...
  79. pmc Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease
    Yazi D Ke
    Alzheimer s and Parkinson s Disease Laboratory, Brain and Mind Research Institute, University of Sydney, Sydney, Australia
    PLoS ONE 4:e7917. 2009
    ..Hence, DM can accelerate onset and increase severity of disease in individuals with a predisposition to developing tau pathology...
  80. 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
    ..Hence, Akt serves as a major regulator of tau biology by manipulating both tau kinases and protein quality control, providing a link to several common pathways that have demonstrated dysfunction in Alzheimer's disease...
  81. doi A mouse model of amyloid beta oligomers: their contribution to synaptic alteration, abnormal tau phosphorylation, glial activation, and neuronal loss in vivo
    Takami Tomiyama
    Departments of Neuroscience, Osaka City University Graduate School of Medicine, Osaka 545 8585, Japan
    J Neurosci 30:4845-56. 2010
    ..These findings suggest that Abeta oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Abeta oligomer-induced pathology in the absence of amyloid plaques...
  82. ncbi Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation
    Markus Schubert
    Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurosci 23:7084-92. 2003
    ..Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease...
  83. ncbi Decreased beta-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease
    Trey Sunderland
    Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA
    JAMA 289:2094-103. 2003
    ..The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid1-42 and tau proteins.
  84. ncbi Alpha-synuclein induces hyperphosphorylation of Tau in the MPTP model of parkinsonism
    Tetyana Duka
    Department of Biochemistry, Molecular and Cellular Biology, Georgetown University, Washington, DC, USA
    FASEB J 20:2302-12. 2006
    ....
  85. doi The pathological process underlying Alzheimer's disease in individuals under thirty
    Heiko Braak
    Department of Neurology, Center for Clinical Research, University of Ulm, Germany
    Acta Neuropathol 121:171-81. 2011
    ..e., before puberty or in early young adulthood...
  86. 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
    ..Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target...
  87. ncbi Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies
    E Kuusisto
    1Department of Neuroscience and Neurology, Section of Neuropathology, University of Kuopio, P O Box 1627, FIN 70211 Kuopio, Finland
    Neuroreport 12:2085-90. 2001
    ....
  88. doi Tau pathophysiology in neurodegeneration: a tangled issue
    Tara L Spires-Jones
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Trends Neurosci 32:150-9. 2009
    ..In particular, based on recent evidence, we propose that a non-apoptotic caspase-associated form of death is occurring in tauopathy...
  89. ncbi Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice
    K Spittaels
    Experimental Genetics Group, Center for Human Genetics, Flemish Institute for Biotechnology, Katholieke Universiteit Leuven, Gasthuisberg O and N 06, B 3000 Leuven, Belgium
    J Biol Chem 275:41340-9. 2000
    ..These findings could have therapeutic implications in the field of neurodegeneration, as discussed...
  90. ncbi Increased level of active GSK-3beta in Alzheimer's disease and accumulation in argyrophilic grains and in neurones at different stages of neurofibrillary degeneration
    K Leroy
    Laboratory of Histology, Neuroanatomy and Neuropathology, Universite Libre de Bruxelles, Campus Erasme, 808 Route de Lennik, B 1070 Brussels, Belgium
    Neuropathol Appl Neurobiol 33:43-55. 2007
    The somatodendritic accumulation of hyperphosphorylated tau proteins is an early event preceding the appearance of neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and might be necessary for their formation...
  91. 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
    ..Our data suggest that tau's amino-terminal projection domain has an important role in neuritic development and establishes tau as a mediator of microtubule-plasma membrane interactions...
  92. pmc Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
    Milos D Ikonomovic
    Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Brain 131:1630-45. 2008
    ..The strong direct correlation of in vivo PiB retention with region-matched quantitative analyses of Abeta plaques in the same subject supports the validity of PiB-PET imaging as a method for in vivo evaluation of Abeta plaque burden...
  93. pmc Physiological release of endogenous tau is stimulated by neuronal activity
    Amy M Pooler
    Department of Neuroscience PO37, King s College London, Institute of Psychiatry, London SE5 8AF, UK
    EMBO Rep 14:389-94. 2013
    ..Tau secretion is therefore a regulatable process, dysregulation of which could lead to the spread of tau pathology in disease...
  94. ncbi Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17
    M Hutton
    Mayo Clinic Jacksonville, Florida 32224, USA
    Nature 393:702-5. 1998
    ..The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17...
  95. doi Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
    Peng Lei
    Mental Health Research Institute, The University of Melbourne, Victoria, Australia
    Nat Med 18:291-5. 2012
    ..These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically...
  96. doi Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines
    Hans Zempel
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    J Neurosci 30:11938-50. 2010
    ..Incipient and local changes similar to those of Abeta oligomers can be evoked by cell stressors (e.g., H(2)O(2), glutamate, serum deprivation), suggesting some common mechanism of signaling...
  97. pmc Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments
    Antonella Caccamo
    Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78245, USA
    J Biol Chem 285:13107-20. 2010
    ..The results presented here provide a molecular basis for the Abeta-induced cognitive deficits and, moreover, show that rapamycin, an FDA approved drug, improves learning and memory and reduces Abeta and Tau pathology...
  98. pmc Prion-like mechanisms in neurodegenerative diseases
    Bess Frost
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Nat Rev Neurosci 11:155-9. 2010
    ..If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block propagation of protein misfolding throughout the brain...
  99. pmc Regulation of tau pathology by the microglial fractalkine receptor
    Kiran Bhaskar
    Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Neuron 68:19-31. 2010
    ..Taken together, our results suggest that CX3CR1 and IL-1/p38 MAPK may serve as novel therapeutic targets for human tauopathies...
  100. pmc Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid
    Michelle E King
    Department of Biology, University of Virginia, Charlottesville, VA 22904, USA
    J Cell Biol 175:541-6. 2006
    ..These results suggest that a seminal cell biological event in AD pathogenesis is acute, tau-dependent loss of microtubule integrity caused by exposure of neurons to readily diffusible Abeta...
  101. pmc Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
    Robert A Rissman
    Institute for Brain Aging and Dementia, University of California, Irvine 92697, USA
    J Clin Invest 114:121-30. 2004
    ..These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline...

Research Grants72

  1. Novel PET imaging agents for early diagnosis of plaque deposition in Alzheimer's
    Padmakar Kulkarni; Fiscal Year: 2010
    ..A successful agent will be highly useful invention not only for early detection of but also for following disease progression and as biomarker for assessing disease-modifying treatments for Alzheimer's disease. ..
  2. Cerebral Malaria: Mechanisms of disease and neurological salvage
    Mahalia S Desruisseaux; Fiscal Year: 2013
    ..Thus, vascular compromise and alterations in Akt and tau may be important in the pathogenesis of malaria and may provide rational targets of drug therapy to ameliorate the consequences of this infection. ..
  3. Novel Hsp90 Inhibitors to Reduce Misfolded Proteins in Alzheimer's Disease
    Mary L Michaelis; Fiscal Year: 2011
    ..Successful completion of this program will advance this concept toward clinical development. ..
  4. A Diarylheptanoid Scaffold to Treat Taopathies
    Chad A Dickey; Fiscal Year: 2013
    ....
  5. Extracellular Zinc Buffering and A-beta Oligomerization
    GUIDO FAAS; Fiscal Year: 2012
    ..With the acquired insight it should be possible to design drugs that specifically target pathological Zn2+ signals that may cause AD while minimally disturbing the Zn2+ signals necessary for normal brain functioning. ..
  6. Tau in cancer cells
    Gloria Lee; Fiscal Year: 2010
    ..The data from this application will further our understanding of how abnormal tau might lead to cell death. ..
  7. Immunotherapy against tauopathy in a transgenic mouse model
    David Morgan; Fiscal Year: 2013
    ..These experiments will use antibodies that bind to the tau protein in an attempt to eliminate it from the brain. This may lead to use of similar antibodies or possible vaccines to treat patients with these diseases. ..
  8. Changing tau Protein Levels and tau Protein Isoforms in Mouse Models of Dementia
    Timothy M Miller; Fiscal Year: 2012
    ..This novel therapeutic strategy, if successful, would be applicable to treating human dementias. ..
  9. TDP-43 acetylation as a pathogenic modification in ALS &related proteinopathies
    TODD JONATHAN COHEN; Fiscal Year: 2013
    ..These innovative studies will highlight TDP-43 acetylation as a critical modification linked to the progression of ALS and related TDP-43 proteinopathies. ..
  10. Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors for
    ALAN D SNOW; Fiscal Year: 2011
    ..Neurofibrillary tangle formation is one of the pathological hallmarks of Alzheimer's disease, the leading cause of dementia in the elderly. ..
  11. MSUT2/SUT2 controls tau protein aggregation and neurotoxicity.
    Brian C Kraemer; Fiscal Year: 2013
    ..If loss of Msut2 suppresses tauopathy in mice, then human MSUT2 is a strong candidate target for therapeutic intervention in diseases with tau pathology. ..
  12. Autophagic Clearance of Aberrant Tau: Biochemical and Therapeutic Implications
    Karen E Duff; Fiscal Year: 2013
    ..or aggregated tau) causes the cell to become dysfunctional, but it is likely that clearing abnormal, misfolded tau proteins will attenuate disease progression and possibly cure, or stabilize the disease...
  13. An iPS Disease-in-a-Dish Model of Familial Alzheimers
    Terrence Town; Fiscal Year: 2012
    ..If successful, this exciting disease-in-a-dish model could allow pre-clinical testing of therapeutic approaches. ..
  14. Autoimmune biomarker profiling in tauopathy
    Irving E Vega; Fiscal Year: 2013
    ..Genetics, biochemical and neuropathological studies suggest that disruption of the biological function of tau proteins, either by mutations, hyperphosphorylation and/or aberrant protein interactions, may play a central role in the ..
  15. Tyrosine Phosphorylation in Alzheimer's Disease
    Gloria Lee; Fiscal Year: 2013
    ..Our data will aid in the identification of new targets for disease therapeutics and new biomarkers for tracking disease progress. ..
  16. Blood-Brain Barrier Disruption in Blast Neurotrauma
    AMANDA DAWN GAUDREAU-BALDERRAMA; Fiscal Year: 2013
    ..Insights gained from this work will stimulate further development of MIMS technology for biomedical research and accelerate translational development of urgently needed diagnostics and therapeutics for blast-related TBI and CTE. ..
  17. Mechanisms of resistance to cognitive decline in AD
    Giulio Taglialatela; Fiscal Year: 2013
    ....
  18. REGULATION OF MRNA PROCESSING
    Phillip A Sharp; Fiscal Year: 2012
    ..These studies will both increase our knowledge of mechanisms controlling alternative splicing and as well the factors that control CD44 activity in diseases such as cancer. ..
  19. A novel therapeutic approach to lowering tau and its impact on tauopathies
    NASSER HUSSEIN ZAWIA; Fiscal Year: 2013
    ....
  20. 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...
  21. Tau Protein Aggregation Inhibitors for Tauopathies
    ALAN D SNOW; Fiscal Year: 2013
    ..This Phase II SBIR project will lead to a pre-clinical candidate (and back-up) for the treatment of tau aggregation in AD and other tauopathies. ..
  22. The role of a novel tau-associated protein in neurodegeneration
    Irving E Vega; Fiscal Year: 2012
    ..Genetics, biochemical and neuropathological studies suggest that disruption of the biological function of tau proteins, either by mutations, hyperphosphorylation and/or aberrant protein interactions, may play a central role in the ..
  23. A Model of Early Alzheimer Disease
    Bradley T Hyman; Fiscal Year: 2012
    ....
  24. Generation of a Transgenic Mouse Model for Functional Study of a Novel Gene FG01
    Huaxi Xu; Fiscal Year: 2010
    ..Moreover, the FG01 transgenic mouse model will have potential in developing novel diagnostic and therapeutic methods for multiple diseases including AD, diabetes and cancers. ..
  25. Deoxyribozymes for Protein Phosphorylation and Dephosphorylation
    Scott K Silverman; Fiscal Year: 2013
    ....
  26. 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 lesions ..
  27. Alzheimer's Disease Cooperative Study (ADCS)
    Paul S Aisen; Fiscal Year: 2012
    ..Our existing minority recruitment core is being expanded into a general recruitment core focused on maximizing the recruitment of minorities and other subjects into our clinical trials. ..
  28. IN VIVO ANALYSIS OF RATIONALLY IDENTIFIED INHIBITOR OF AMYLOID B_PROTEIN ASSEMBLY
    AIDA ATTAR; Fiscal Year: 2012
    ..We address this urgent need by assessing the utility, in an animal model, of an innovative small molecule inhibitor of amyloid 2-protein assembly, which has a novel mechanism of action and has proven effective in vitro. ..
  29. Epitope-Specific Targeting of Tau Aggregates.
    Einar M Sigurdsson; Fiscal Year: 2013
    ..The important structural information can also facilitate development of small molecule mimetics for therapeutic or diagnostic use. Together, these aims may lead to a novel therapy for AD and related tauopathies. ..
  30. The Impact Of Prolonged Anesthetic Exposure On Tau Pathology And Function
    Robert A Whittington; Fiscal Year: 2013
    ..This information is critical for attaining the long-term goal of preventing an acceleration of tau pathology and cognitive impairment in the growing number of patients, with or at risk for AD, who require anesthesia. ..
  31. The Hsp90 cochaperone FKBP51 regulates tau structure and function
    Chad A Dickey; Fiscal Year: 2013
    ..These studies may lead to drug development that can provide sufferers of tauopathies a way to combat their condition, with the ultimate goal being a cure. ..
  32. Chaperone-mediated signaling in Alzheimer's disease
    Chad A Dickey; Fiscal Year: 2010
    ..Specifically, we intend to focus on the removal of the proteins once they have already started to accumulate in an effort to reverse the progression of the disease rather than prevent it. ..
  33. Genomic Analysis of Alzheimer's Disease Genes
    GERARD DAVID SCHELLENBERG; Fiscal Year: 2013
    ..Likewise, identification of trans-factors may lead to protein targets such as kinases that are also therapeutic targets. ..
  34. IBMPFD MUTATIONS IMPAIR UPS FUNCTION
    Conrad C Weihl; Fiscal Year: 2013
    ..Although a rare disorder, the study of IBMPFD is essential to understand the role of the UPS in normal aging and aging related disorders such as sIBM and FTD. ..
  35. Pharmacological modulation of tau neurotoxicity in vivo
    Mel B Feany; Fiscal Year: 2012
    ..We anticipate that the well- characterized nature of the compounds will facilitate translation of these therapeutic compounds to testing in vertebrate animal models and to eventual use in the clinic. ..
  36. O-GlcNAcylation of tau: a link between glucose metabolism and neurodegeneration
    Cheng Xin Gong; Fiscal Year: 2010
    ..Completion of these studies will provide new insight into the mechanism of neurodegeneration of AD and help develop novel strategies to prevent and treat AD and probably other neurodegenerative disorders. ..
  37. INVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASE
    JOEL SYNES PERLMUTTER; Fiscal Year: 2013
    ..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. Biomarkers for White Matter Injury in Mixed and Vascular Cognitive Impairment
    GARY ALLEN ROSENBERG; Fiscal Year: 2013
    ..This aim is focused on determining the implications of amyloid and tau proteins in the CSF of SIVD patients...
  39. Hyperphosphorylated tau as drug target
    Min Hao Kuo; Fiscal Year: 2012
    ....
  40. SPECIFICITY OF DOMAIN INTERACTIONS IN CELL SIGNALING
    Mark A Lemmon; Fiscal Year: 2010
    ..In parallel, we will map orthologous interactions in mammalian cells, establishing a new paradigm for PH domains that resembles the role of SH2, and SH3 domains. ..
  41. Pesticide-mediated inhibition of UBA1 and cumulative risk for Parkinson's Disease
    William M Valentine; Fiscal Year: 2013
    ..and increased UBA1 function on viability, the expression and phosphorylation state of -synuclein and tau proteins, activation of Cdk5 and expression and localization of the dopamine transporter in cells exposed to the ..
  42. Brain aging and treatment response in geriatric depression
    Helen Lavretsky; Fiscal Year: 2013
    ..Our study will provide unique information on the use of memantine in geriatric depression, and will investigate the underlying mechanism of treatment response, and subgroups with preferential treatment to memantine. ..
  43. Tracking the Propagation of Misfolded Tau: A Study of Cellular Uptake and Traffic
    BRANDON BLAKE HOLMES; Fiscal Year: 2013
    ..These studies will help delineate the cellular environment in which tau aggregates convert natively folded tau into an aggregated, fibrillar form. ..
  44. ALZHEIMERS DISEASE RESEARCH CENTER
    John Morris; Fiscal Year: 2013
    ..Changing tau protein levels and tau protein isoforms in mouse models of dementia;(Timothy Miller) 3. APOE metabolism in AD and controls;(Randall Bateman). ..
  45. Developing neuroprotective strategies for proteinopathy: a comparative modeling
    Brian C Kraemer; Fiscal Year: 2013
    ..The long term goal of this work is to develop neuroprotective strategies for neurodegenerative disorders with TPD-43 and tau protein deposits. ..
  46. Novel Stem Cell and Mouse Models to Study Frontotemporal Dementia
    MIRANDA ETHEL ORR; Fiscal Year: 2010
    ..If neurospheres recapitulate in vivo phenotypes of their parent mouse strains, they may serve as high through-put assay systems to investigate other genes and small molecules involved in disease pathogenesis. ..
  47. Tau and Glutamatergic Synapses in Frontotemporal Dementia
    Brian A Warmus; Fiscal Year: 2013
    ..The results from this proposal will help identify potential treatment targets and help direct future studies on the causes, prevention, and treatment of FTD. ..
  48. Biological and Pathological Interactions between Tau and LRRK2
    JADA M LEWIS; Fiscal Year: 2013
    ....
  49. Probing early protein aggregation mechanisms and their relationship to disease ef
    SongI Han; Fiscal Year: 2011
    ..We will work with the two full length human isoforms, tau-3R and tau-4R, as well as the caspase-cleaved tau proteins, as has been recently found to precede tangle formation in vivo...
  50. CELL-CELL TRANSFER AND PROPAGATION OF TAU AGGREGATES
    Marc I Diamond; Fiscal Year: 2013
    ..This research will help solve these problems, as it is focused on understanding the cellular mechanisms that influence pathogenesis. ..
  51. Genetic Determinants of Tauopathies
    Jason Chen; Fiscal Year: 2013
    ..By performing this work, we will discover genetic factors that contribute to tauopathies and the mechanisms by which they operate, findings of diagnostic and therapeutic significance. ..
  52. Delineating conformational variants of the Abeta peptide
    Joel Watts; Fiscal Year: 2013
    ....
  53. Phase 11-Grape Seed Extract as Anti-Oligomerization Agent in Alzheimer's Disease
    Hillel Grossman; Fiscal Year: 2012
    ..In the brain, monomeric Ab peptides and tau proteins are aggregated to form high molecular weight, soluble multimeric neurotoxic Ab and tau species...
  54. Contribution of Multisensory Stimuli on Entorhinal Circuit Dynamics and the Menta
    ASHLEY LINDA KEES; Fiscal Year: 2013
    ..Understanding the circuitry in the healthy brain will provide more traction in tackling complex psychiatirc disorders. ..
  55. Alpha4's regulation of PP2A activity: Role in tau hyperphosphorylation
    MICHELE LAURA LENOUE-NEWTON; Fiscal Year: 2013
    ..The goal of this project is to elucidate the mechanism of alpha4 regulation of PP2A and investigate the role alpha4 plays in regulating PP2A activity towards tau. ..
  56. Generation of Tau Prion Strains in Dividing Mammalian Cells
    DAVID WINLAND SANDERS; Fiscal Year: 2013
    ..research is significan because it could help lead to more accurate diagnosis of tauopathies, and to more precise antibody-based treatments that target extracellular protein, which are gaining increasing attention as potential therapies ..
  57. Neuroimaging Biomarkers in Mouse Models of AD
    Robia G Pautler; Fiscal Year: 2012
    ..Third, we will determine if Ab1- 40, Ab1-42 or the combination of the two species contributes to in vivo changes in axonal transport and pre- synaptic release and post-synaptic uptake mechanisms in mouse models of AD. ..
  58. In vivo neurophysiological study of a neurodegenerative mouse model
    Daoyun Ji; Fiscal Year: 2013
    ..abstract_text> ..
  59. AGING AND ALZHEIMER DEMENTIA--ROLE OF FIBROUS PROTEINS
    Shu Hui Yen; Fiscal Year: 2000
    ....
  60. Genome-wide analysis of tau neurotoxicity
    Mel B Feany; Fiscal Year: 2013
    ....
  61. Tau polymerization as a target for Alzheimer's disease
    TRUMAN C GAMBLIN; Fiscal Year: 2010
    ..I feel that this time will greatly increase the productivity in the laboratory and enhance the development of my career. ..
  62. Biochemical and in vivo determinants of tau neurotoxicity
    TRUMAN C GAMBLIN; Fiscal Year: 2013
    ..We will now combine our strengths in biochemistry and in vivo tauopathy modeling to define the species of tau that cause cellular and organismal toxicity in tauopathies. ..
  63. PATHOBIOLOGY OF TAU PROTEIN
    KENNETH KOSIK; Fiscal Year: 1999
    ..Saporin is toxic to cells only when it reaches the cytosol. ..
  64. MECHANISMS OF OCCUPATIONAL NEUROPATHIES
    MOHAMED ABOU DONIA; Fiscal Year: 1999
    ....
  65. PET IMAGING PROBES FOR AMYLOID IN ALZHEIMERS AND AGING
    William Klunk; Fiscal Year: 2005
    ....
  66. Designed Inhibitors of Pin1 in Mitosis
    FELICIA ETZKORN; Fiscal Year: 2009
    ..The best ligands will be useful in collaborations designed to elucidate the structure, function and dynamic relationships within Pin1 and between Pin1 and its ligands. ..
  67. PET TRACERS TO MONITOR VACCINE AND IMMUNE THERAPY FOR AD
    William Klunk; Fiscal Year: 2005
    ....
  68. Progression of Tau Pathology in AD
    Lester Binder; Fiscal Year: 2007
    ..Using gene array technology, we propose to determine the relative quantities of CK1 message and the amounts of caspase message in individual CBF neurons from patients with the aforementioned clinical diagnoses. ..
  69. STRUCTURE AND FUNCTION OF MOUSE TAU PROTEIN
    Gloria Lee; Fiscal Year: 1992
    ..The specific aims of this work are: 1) to determine the complete amino acid sequence of two distinct mouse tau proteins, based on cDNA clones previously obtained from 6 day mice, and to identify areas of heterogeneity; 2) to ..
  70. BIOCHEMISTRY AND PATHOBIOLOGY OF MAP TWO IN NEURONS
    KENNETH KOSIK; Fiscal Year: 1990
    ..MAP2 and tau cDNA probes will be used to demonstrate ribosomal topography and their possible contribution of the compartmentalization. Finally, we propose to initiate dynamic studies of possible roles for the MAPs in neuronal transport...
  71. Modeling Human Tauopathies in Drosophila melanogaster
    Gena Heidary; Fiscal Year: 2003
    ..abstract_text> ..
  72. MECHANISM AND CONTROL OF BRAIN MICROTUBULE DYNAMICS
    Leslie Wilson; Fiscal Year: 2009
    ..It will involve determination how the tau proteins, which stabilize microtubules and may mis-regulate dynamics in neurodegenerative tauopathies such as ..