tauopathies

Summary

Summary: Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.

Top Publications

  1. pmc Brain homogenates from human tauopathies induce tau inclusions in mouse brain
    Florence Clavaguera
    Department of Neuropathology, Institute of Pathology, University Hospital, 4031 Basel, Switzerland
    Proc Natl Acad Sci U S A 110:9535-40. 2013
  2. 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
  3. ncbi Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L)
    Martin Ramsden
    Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    J Neurosci 25:10637-47. 2005
  4. 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
  5. 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
  6. ncbi 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
  7. pmc MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies
    Daniah Trabzuni
    Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Hum Mol Genet 21:4094-103. 2012
  8. 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
  9. 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
  10. pmc Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy
    Tara L Spires
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown 02129, USA
    Am J Pathol 168:1598-607. 2006

Detail Information

Publications306 found, 100 shown here

  1. pmc Brain homogenates from human tauopathies induce tau inclusions in mouse brain
    Florence Clavaguera
    Department of Neuropathology, Institute of Pathology, University Hospital, 4031 Basel, Switzerland
    Proc Natl Acad Sci U S A 110:9535-40. 2013
    ..Here we injected brain extracts from humans who had died with various tauopathies into the hippocampus and cerebral cortex of ALZ17 mice...
  2. 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
    ..Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease...
  3. ncbi Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L)
    Martin Ramsden
    Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    J Neurosci 25:10637-47. 2005
    ..Collectively, these data describe a novel transgenic mouse that closely mimics human tauopathy and may represent an important model for the future study of tau-related neurodegenerative disease...
  4. 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
    b>Tauopathies are a class of neurodegenerative diseases marked by intracellular aggregates of hyperphosphorylated Tau...
  5. 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
    Neurofibrillary tangles (NFTs) in Alzheimer disease and related tauopathies are composed of insoluble hyperphosphorylated Tau protein, but the mechanisms underlying the conversion of highly soluble Tau into insoluble NFTs remain elusive...
  6. ncbi 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
    ..tau is integral to the pathogenesis of Alzheimer's disease (AD), as well as several related disorders, termed tauopathies, in which tau is deposited in affected brain regions...
  7. pmc MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies
    Daniah Trabzuni
    Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Hum Mol Genet 21:4094-103. 2012
    ....
  8. 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
    The accumulation of insoluble proteins is a pathological hallmark of several neurodegenerative disorders. Tauopathies are caused by the dysfunction and aggregation of tau protein and an impairment of cellular protein degradation pathways ..
  9. 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...
  10. pmc Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy
    Tara L Spires
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown 02129, USA
    Am J Pathol 168:1598-607. 2006
    ..Together, these results imply that neurofibrillary tangles do not necessarily lead to neuronal death...
  11. 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
    ....
  12. 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
    Neurofibrillary tangles (NFTs) are a pathological hallmark of Alzheimer's disease and other tauopathies, but recent studies in a conditional mouse model of tauopathy (rTg4510) have suggested that NFT formation can be dissociated from ..
  13. ncbi Mutations causing neurodegenerative tauopathies
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Biochim Biophys Acta 1739:240-50. 2005
    ..of experimental animal models that reproduce the essential molecular and cellular features of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and nerve cell ..
  14. ncbi Tau alternative splicing in familial and sporadic tauopathies
    Michael Niblock
    Department of Clinical Neuroscience, Institute of Psychiatry, King s College London, London, UK
    Biochem Soc Trans 40:677-80. 2012
    ..Tau alternative splicing could represent a target for therapeutic intervention to delay the progression of pathology in familial as well as sporadic tauopathies.
  15. ncbi The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy
    Katrin Eckermann
    Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany
    J Biol Chem 282:31755-65. 2007
    Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau...
  16. pmc mTOR regulates tau phosphorylation and degradation: implications for Alzheimer's disease and other tauopathies
    Antonella Caccamo
    Department of Physiology and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
    Aging Cell 12:370-80. 2013
    Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia...
  17. pmc Tau in Alzheimer disease and related tauopathies
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    Curr Alzheimer Res 7:656-64. 2010
    ..Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
  18. ncbi Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease
    Masashi Kitazawa
    Department of Neurobiology and Behavior, University of California Irvine, California 92697 4545, USA
    J Neurosci 25:8843-53. 2005
    ..Therefore, this study clearly demonstrates that microglial activation exacerbates key neuropathological features such as tangle formation...
  19. ncbi Tau pathology in Alzheimer disease and other tauopathies
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Biochim Biophys Acta 1739:198-210. 2005
    ..It is this pathology which is characteristic of Alzheimer disease (AD) and other tauopathies. To date, the most established and the most compelling cause of dysfunctional tau in AD and other tauopathies ..
  20. pmc Analysis of tau phosphorylation and truncation in a mouse model of human tauopathy
    Patrice Delobel
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK
    Am J Pathol 172:123-31. 2008
    ..and may be necessary for the assembly of tau into filaments in Alzheimer's disease and other tauopathies. Here we have investigated the time course of the appearance of phosphorylated and truncated tau in the brain ..
  21. 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
    ..the hyperphosphorylated microtubule-associated protein tau (MAPT) are an invariant neuropathological feature of tauopathies. Here, we show that microglial neuroinflammation promotes MAPT phosphorylation and aggregation...
  22. pmc Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice
    Tristan Bolmont
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, Otfried Müller Str 27, D 72076 Tubingen, Germany
    Am J Pathol 171:2012-20. 2007
    ....
  23. pmc Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy
    Brian C Kraemer
    Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108 1597, USA
    Proc Natl Acad Sci U S A 100:9980-5. 2003
    ..soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in FTDP-17, AD, and other tauopathies. Substantial neurodegeneration, seen as bulges and gaps in nerve cords followed by loss of neurons, occurs ..
  24. pmc Tau and tauopathies
    Gloria Lee
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    Prog Mol Biol Transl Sci 107:263-93. 2012
    b>Tauopathies are age-related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau...
  25. ncbi Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease
    Manuela Neumann
    Institute of Neuropathology, Ludwig Maximilians University of Munich, Munich, Germany
    Acta Neuropathol 107:489-96. 2004
    ..antibodies against DJ-1, we have performed a comprehensive investigation of DJ-1 in alpha-synucleinopathies and tauopathies. DJ-1 was abundantly expressed in reactive astrocytes of patients with neurodegenerative diseases...
  26. pmc The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features
    Eleanna Kara
    Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK
    Neurobiol Aging 33:2231.e7-2231.e14. 2012
    ..tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p...
  27. ncbi A new link to mitochondrial impairment in tauopathies
    Kathrin L Schulz
    Department of Pharmacology, ZAFES, Biocenter, University of Frankfurt, 60438 Frankfurt, Germany
    Mol Neurobiol 46:205-16. 2012
    b>Tauopathies like the "frontotemporal dementia with Parkinsonism linked to chromosome 17" (FTDP-17) are characterized by an aberrant accumulation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau...
  28. ncbi Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies
    Connie Luk
    Reta Lila Weston Institute, UCL Institute of Neurology, London, UK
    J Neurochem 123:396-405. 2012
    Characteristic tau isoform composition of the insoluble fibrillar tau inclusions define tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal dementia with parkinsonism linked to ..
  29. pmc Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathies
    Tara Vanderweyde
    Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118 2526, USA
    J Neurosci 32:8270-83. 2012
    ....
  30. ncbi Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability
    Laura Gasparini
    Cambridge Centre for Brain Repair, The University of Cambridge, Robinson Way, Forvie Site, Cambridge CB2 0PY, UK
    Neurobiol Aging 32:419-33. 2011
    Tau inclusions play a key role in the pathogenesis of tauopathies. Altered tau levels have been detected in retina and optic nerve of patients with glaucoma, suggesting the possibility of shared pathogenic mechanisms with tauopathies...
  31. pmc AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathies
    Valérie Vingtdeux
    Litwin Zucker Research Center for the Study of Alzheimer s Disease, The Feinstein Institute for Medical Research, North Shore LIJ, 350 Community Drive, Manhasset, NY 11030, USA
    Acta Neuropathol 121:337-49. 2011
    b>Tauopathies represent a class of neurodegenerative disorders characterized by abnormal tau phosphorylation and aggregation into neuronal paired helical filaments (PHFs) and neurofibrillary tangles...
  32. 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
    ..our understanding of the mechanisms of tau-mediated neurodegeneration in Alzheimer's disease (AD) and related tauopathies, which are characterized by prominent CNS accumulations of fibrillar tau inclusions, are rapidly moving this ..
  33. pmc Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
    David J Irwin
    Centre for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer s Disease Core Centre, Institute on Ageing, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6021, USA
    Brain 135:807-18. 2012
    ..component of neurofibrillary inclusions characteristic of Alzheimer's disease and related neurodegenerative tauopathies. When tau fibrillizes, it undergoes abnormal post-translational modifications resulting in decreased solubility ..
  34. ncbi Comparison of family histories in FTLD subtypes and related tauopathies
    J S Goldman
    Memory and Aging Center, University of California, San Francisco, CA 94117, USA
    Neurology 65:1817-9. 2005
    ..FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks...
  35. pmc Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies
    Kunihiro Uryu
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Neuropathol Exp Neurol 67:555-64. 2008
    ..These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis...
  36. pmc Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104 4283, USA
    Nat Rev Drug Discov 8:783-93. 2009
    ..of the microtubule-associated protein tau are found in numerous neurodegenerative diseases, commonly known as tauopathies. In Alzheimer's disease - the most prevalent tauopathy - misfolded tau is probably a key pathological agent...
  37. ncbi Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic mice
    Dick Terwel
    Experimental Genetics Group, Department of Human Genetics, KU Leuven, B 3000 Leuven, Belgium
    J Biol Chem 280:3963-73. 2005
    ..phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration...
  38. ncbi Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies
    R De Silva
    Reta Lila Weston Institute of Neurological Studies, University College London, and Department of Molecular Neuroscience and Neuropathology, Institute of Neurology, UK
    Neuropathol Appl Neurobiol 29:288-302. 2003
    ..containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17),..
  39. ncbi The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts
    Amanda J Myers
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892 3707, USA
    Neurobiol Dis 25:561-70. 2007
    ..We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.
  40. ncbi Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: possible implications for tauopathies and Alzheimer's disease
    Clement Menuet
    Maturation, Plasticity, Physiology and Pathology of Respiration MP3 Respiration, Unité Mixte de Recherche 6231, Centre National de la Recherche Scientifique, Universite de la Mediterranee, Universite Paul Cezanne, Faculté Saint Jérôme Service 362, 13397 Marseille Cedex 20, France
    Respir Physiol Neurobiol 178:290-303. 2011
    b>Tauopathies, including Alzheimer's disease are the most frequent neurodegenerative disorders in elderly people...
  41. ncbi The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies
    Diana A T Nijholt
    Department of Genome Analysis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Pathol 226:693-702. 2012
    ..The aim of the present study is to investigate UPR activation in sporadic tauopathies like progressive supranuclear palsy (PSP) and Pick's disease (PiD), and familial cases with frontotemporal ..
  42. ncbi Assembly of tau in transgenic animals expressing P301L tau: alteration of phosphorylation and solubility
    Naruhiko Sahara
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
    J Neurochem 83:1498-508. 2002
    ..The results suggest that tau in S2 represents an intermediate from which insoluble tau is derived, and that phosphorylation may play a role in filament formation and/or stabilization...
  43. pmc Distinct tau prion strains propagate in cells and mice and define different tauopathies
    David W Sanders
    Department of Neurology, Washington University in St Louis, St Louis, MO 63105, USA
    Neuron 82:1271-88. 2014
    Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations ("strains") in vivo that link structure to patterns of pathology...
  44. ncbi Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy
    Moran Boimel
    Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    J Neuropathol Exp Neurol 68:314-25. 2009
    ..Statins may provide therapy against NFTs in tauopathies, particularly when NFTs are the major neuropathologic component.
  45. ncbi "Prion-like" templated misfolding in tauopathies
    Florence Clavaguera
    Department of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland
    Brain Pathol 23:342-9. 2013
    ..insoluble and filamentous inclusions in a number of neurodegenerative diseases referred to as "tauopathies." In Alzheimer's disease, tau pathology develops in a stereotypical manner, with the first lesions appearing in ..
  46. ncbi Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice TgTauP301L
    Atsushi Sasaki
    Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma, Japan
    Brain Res 1214:159-68. 2008
    ..to phosphorylated tau accumulation and the characteristics of microglial activation in brain lesions of human tauopathies in comparison to mutant tau transgenic (TG) mice...
  47. pmc Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 30:13861-6. 2010
    ..Accordingly, a possible therapeutic strategy for AD and related "tauopathies" is treatment with a MT-stabilizing anti-cancer drug such as paclitaxel...
  48. pmc Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutation
    Wen Lang Lin
    Mayo Clinic, Jacksonville, Florida, USA
    Am J Pathol 162:213-8. 2003
    ..Given similarities of the lesions in the mice to human neuronal and glial inclusions, these transgenic mice appear to be a valuable model to study pathogenesis of the neurodegenerative tauopathies.
  49. ncbi Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspects
    Natalia Shiryaev
    The Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv 69978, Israel
    Curr Pharm Des 17:2603-12. 2011
    ..These studies associate neuroprotection in vivo and in vitro and provide a broad base for future drug development based on NAP and D-SAL against multiple neurodegenerative conditions...
  50. ncbi An okadaic acid-induced model of tauopathy and cognitive deficiency
    Zhang Zhang
    Deptment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
    Brain Res 1359:233-46. 2010
    ....
  51. pmc Transgenic Drosophila models of Alzheimer's disease and tauopathies
    Kanae Iijima-Ando
    Laboratory of Neurogenetics and Pathobiology, Department of Biochemistry and Molecular Biology, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, JHN410, Philadelphia, PA, 19107, USA
    Brain Struct Funct 214:245-62. 2010
    ..dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases, so called tauopathies. Although most cases are sporadic, genes associated with familial AD and FTDP-17 have been identified, which ..
  52. ncbi Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies
    Hanae Nakashima
    Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 700 8558, Okayama, Japan
    Acta Neuropathol 110:547-56. 2005
    ..Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation...
  53. ncbi Cell-mediated neuroprotection in a mouse model of human tauopathy
    David W Hampton
    Euan MacDonald Centre for Motor Neurone Disease Research, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    J Neurosci 30:9973-83. 2010
    ..Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau...
  54. pmc Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain
    Allal Boutajangout
    Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
    J Neurochem 118:658-67. 2011
    Targeting hyperphosphorylated tau by immunotherapy is emerging as a promising approach to treat tauopathies such as Alzheimer's disease and frontotemporal dementia...
  55. ncbi Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation
    Jose A Rodriguez-Navarro
    Department of Neurobiology, Hospital Ramon y Cajal, and CIBERned Madrid, Spain
    Neurobiol Dis 39:423-38. 2010
    b>Tauopathies are neurodegenerative diseases, sporadic or familial, mainly characterized by dementia and parkinsonism associated to atrophy of the frontotemporal cortex and the basal ganglia, with deposition of abnormal tau in brain...
  56. ncbi Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expression
    Tadanori Hamano
    Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA
    Eur J Neurosci 27:1119-30. 2008
    ..pathological hallmark shared by Alzheimer's disease and other neurodegenerative disorders known collectively as tauopathies. To model how tau fibrillogenesis evolves in tauopathies, we previously established transfectant M1C cultures ..
  57. ncbi Tau pathology and future therapeutics
    I Gozes
    Laboratory for Molecular Neuroendocrinology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Curr Alzheimer Res 7:685-96. 2010
    ....
  58. pmc Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model
    Leora M Fox
    Massachusetts General Hospital Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, 02129, USA
    J Neuropathol Exp Neurol 70:588-95. 2011
    Neurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and although they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal ..
  59. ncbi Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nuclei
    Mathias Dutschmann
    Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    J Neurosci 30:1810-21. 2010
    ..Some primary tauopathies are linked to mutations in the MAPT gene coding for protein tau, but most are sporadic with unknown causes...
  60. pmc Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies
    Tomas L Falzone
    Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Hum Mol Genet 19:4399-408. 2010
    ..hyperphosphorylation and aggregation of the microtubule-associated protein tau defines neurodegenerative tauopathies. Destabilization of microtubules by loss of tau function and filament formation by toxic gain of function are ..
  61. ncbi Alzheimer's disease: old problem, new views from transgenic and viral models
    Tomasz Jaworski
    Experimental Genetics Group, LEGTEGG, Dept Human Genetics, KULeuven Campus Gasthuisberg ON1 06 602, Herestraat 49, B 3000 Leuven, Belgium
    Biochim Biophys Acta 1802:808-18. 2010
    ..We focus on specific aspects of single and multiple transgenic mouse models for Alzheimer's disease and for tauopathies, rather than providing an exhaustive list of all available models...
  62. ncbi Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy
    Karin Boekhoorn
    Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1098 SM Amsterdam, The Netherlands
    J Neurosci 26:3514-23. 2006
    The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations in the tau gene...
  63. ncbi Interneuronal transfer of human tau between Lamprey central neurons in situ
    Wonhee Kim
    Department of Biological Sciences, Center for Cellular Neuroscience and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA, USA
    J Alzheimers Dis 19:647-64. 2010
    ..interconnected parts of the brain are a potentially important but poorly understood component of human tauopathies such as Alzheimer's disease, Pick's disease, and corticobasal degeneration...
  64. ncbi Disentangling the role of the tau gene locus in sporadic tauopathies
    J Vandrovcova
    Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK
    Curr Alzheimer Res 7:726-34. 2010
    ..neurofibrillary tangles that define the broad class of late-onset neurodegenerative disorders called the tauopathies. Mutations in the tau gene (MAPT) causing familial frontotemporal dementia with parkinsonism linked to ..
  65. ncbi Important neuronal toxicity of microtubule-bound Tau in vivo in Drosophila
    Yasmina Talmat-Amar
    CNRS, UMR 5203, Institut de Genomique Fonctionnelle, 141 rue de la Cardonille, Montpellier, France
    Hum Mol Genet 20:3738-45. 2011
    ..Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease...
  66. ncbi Unclassifiable tauopathy associated with an A152T variation in MAPT exon 7
    G G Kovacs
    Institute of Neurology, Medical University of Vienna, Vienna, Austria
    Clin Neuropathol 30:3-10. 2011
    ..Our observation of an apparently familial disorder with a novel neuropathological phenotype suggests a possible pathogenic role of this MAPT gene variation, which might be different from mutations affecting the microtubule binding...
  67. ncbi Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies
    R Constantinescu
    Department of Neurology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden
    Acta Neurol Scand 127:e8-12. 2013
    ..Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA)...
  68. ncbi Tau oligomers as potential targets for immunotherapy for Alzheimer's disease and tauopathies
    C A Lasagna-Reeves
    George P and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555 0857, USA
    Curr Alzheimer Res 8:659-65. 2011
    ..of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD; specifically, aggregates of a size intermediate between monomers ..
  69. pmc Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathies
    Adriana Ferreira
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
    Mol Med 17:676-85. 2011
    Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected ..
  70. ncbi Cascade of tau toxicity in inducible hippocampal brain slices and prevention by aggregation inhibitors
    Lars Messing
    German Center for Neurodegenerative Diseases DZNE, Bonn, Germany
    Neurobiol Aging 34:1343-54. 2013
    Mislocalization and aggregation of the axonal protein tau are hallmarks of Alzheimer's disease and other tauopathies. Here, we studied the relationship between tau aggregation, loss of spines and neurons, and reversibility by aggregation ..
  71. pmc Rapid accumulation of endogenous tau oligomers in a rat model of traumatic brain injury: possible link between traumatic brain injury and sporadic tauopathies
    Bridget E Hawkins
    Sealy Center for Vaccine Development University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 288:17042-50. 2013
    ..These findings suggest that diagnostic tools and therapeutics that target only toxic forms of Tau may provide earlier detection and safe, more effective treatments for tauopathies associated with repetitive neurotrauma.
  72. ncbi Mechanistic studies unravel the complexity inherent in tau aggregation leading to Alzheimer's disease and the tauopathies
    Gayathri Ramachandran
    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India
    Biochemistry 52:4107-26. 2013
    ..of the protein tau into amyloid fibrils is known to be involved in the causation of the neurodegenerative tauopathies and the progression of cognitive decline in Alzheimer's disease...
  73. ncbi Targeting heat shock proteins in tauopathies
    M DeTure
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Curr Alzheimer Res 7:677-84. 2010
    ..This review discusses the recent advances of the roles of heat shock proteins in this process...
  74. ncbi Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies
    Makoto Higuchi
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104
    J Neurosci 25:9434-43. 2005
    Abundant filamentous tau inclusions in oligodendrocytes (OLGs) are hallmarks of neurodegenerative tauopathies, including sporadic corticobasal degeneration and hereditary frontotemporal dementia with parkinsonism linked to chromosome 17 (..
  75. ncbi Posttranslational modifications of tau--role in human tauopathies and modeling in transgenic animals
    Feng Chen
    Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland
    Curr Drug Targets 5:503-15. 2004
    ..of scant or no beta-amyloid plaques characterizes additional neurodegenerative disorders collectively called tauopathies. In the course of plaque and NFT formation, the major proteinaceous components of these lesions undergo post-..
  76. ncbi Ultrastructural characteristics of tau filaments in tauopathies: immuno-electron microscopic demonstration of tau filaments in tauopathies
    Kunimasa Arima
    Department of Laboratory Medicine, Musashi Hospital, National Center of Neurology and Psychiatry, 4 1 1, Ogawahigashi, Kodaira, Tokyo 187 8551, Japan
    Neuropathology 26:475-83. 2006
    ..In sporadic tauopathies, individual tau filaments show characteristic sizes, shapes and arrangements, and therefore contribute to ..
  77. pmc Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory
    Julio J Ramirez
    Department of Psychology, Davidson College, Davidson, NC 28035, USA
    Behav Brain Res 216:332-40. 2011
    ..Thus, highly restricted vector-induced tauopathy in retrohippocampal areas is sufficient for producing progressive impairment in mnemonic ability in rats, successfully mimicking a key aspect of tauopathies such as AD.
  78. ncbi A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoring
    Dana Krinke
    Centre for Biotechnology and Biomedicine BBZ, University of Leipzig, Division of Molecular Biological Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany
    Biosens Bioelectron 26:162-8. 2010
    ..Moreover, we were able to detect and quantify distinct, AD-related effects triggered by tau-mutant (P301L) expression and hyperphosphorylation in our organotypic 3D-cultures with the help of impedance spectroscopy...
  79. pmc Is tau ready for admission to the prion club?
    Garth F Hall
    Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA, USA
    Prion 6:223-33. 2012
    ....
  80. ncbi 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
    Tau is a neuronal microtubule-associated protein involved in microtubules assembly and stabilization. Tauopathies, including Alzheimer's disease and fronto-temporal dementia with parkinsonism linked to chromosome 17, are a group of ..
  81. pmc Modulation of protein-protein interactions as a therapeutic strategy for the treatment of neurodegenerative tauopathies
    C Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th St, Philadelphia, PA 19104 6323, USA
    Curr Top Med Chem 11:317-30. 2011
    ..and unresolved issues surrounding the development of novel therapeutics for the treatment of neurodegenerative tauopathies, which are based on (A) MT-stabilizing agents to compensate for the loss of normal tau function, and (B) small ..
  82. 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
    ..In general, aggregation propensity correlated with genetic risk reported for multiple tauopathies, implicating aggregation as one candidate mechanism rationalizing the correlation between Tau expression ..
  83. ncbi Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1
    Ji Wu Wang
    Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education, and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
    J Neurosci 27:574-81. 2007
    ..These results reveal a new function for the tumor suppressor protein LKB1 in a signaling cascade through which the phosphorylation and function of tau is regulated by diverse signals under physiological and pathological conditions...
  84. pmc Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy
    Michiyo Iba
    Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 33:1024-37. 2013
    b>Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau pathologies, are neurodegenerative diseases characterized by neurofibrillary tangles (NFTs) comprising filamentous tau protein...
  85. ncbi Pathogenesis of the tauopathies
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    J Mol Neurosci 45:425-31. 2011
    ..However, most tauopathies are not inherited in a dominant manner...
  86. ncbi Filamin-A and Myosin VI colocalize with fibrillary Tau protein in Alzheimer's disease and FTDP-17 brains
    Sébastien Feuillette
    INSERM U614, Institute for Biomedical Research, Faculty of Medicine, University of Rouen, Rouen, France
    Brain Res 1345:182-9. 2010
    b>Tauopathies, including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease and progressive supranuclear palsy, are neurodegenerative disorders neuropathologically ..
  87. pmc Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice
    Dick Terwel
    Experimental Genetics Group, Department Human Genetics, Katholieke Universiteit Leuven Campus Gasthuisberg ON1 06 602, B 3000 Leuven, Belgium
    Am J Pathol 172:786-98. 2008
    ..The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons...
  88. pmc Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options
    A C Ludolph
    Department of Neurology, University of Ulm, Ulm, Germany
    Eur J Neurol 16:297-309. 2009
    b>Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system...
  89. ncbi Tauopathies
    F Hernandez
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Fac Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
    Cell Mol Life Sci 64:2219-33. 2007
    ..of its isoforms could provoke pathological effects resulting in the appearance of neuronal disorders known as tauopathies. The purpose of this work is to review the possible mechanisms for tau alterations that could lead to the onset ..
  90. ncbi Tau and tauopathies
    M Robert
    Department of Neurology, Medical College, Trivandrum, Kerala, India
    Neurol India 55:11-6. 2007
    ..neuronal, oligodendroglial or astrocytic filamentous tau inclusions are now grouped under the common rubric of tauopathies. The discovery of mutations in the tau gene, located on Chromosome 17 and its relationship to frontotemporal ..
  91. 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
    In Alzheimer 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...
  92. ncbi The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy
    Günter U Höglinger
    INSERM U679, Hopital de la Salpetriere, Paris, France
    J Neurochem 95:930-9. 2005
    ..Our data suggest that chronic respiratory chain dysfunction might trigger a form of neurodegeneration in which accumulation of hyperphosphorylated tau protein predominates over deposits of alpha-synuclein...
  93. ncbi Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau
    Wen Lang Lin
    Mayo Clinic, Jacksonville, Florida 32224, USA
    J Neurocytol 32:1091-105. 2003
    ..The other type resembled ballooned neurons seen in some human tauopathies. The nucleus was peripherally placed, but normal appearing...
  94. 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
    ..CHIP could rescue phosphorylated tau-induced cell death, and therefore the CHIP-Hsc70 complex may provide a new therapeutic target for the tauopathies.
  95. ncbi Progressive neurodegeneration in C. elegans model of tauopathy
    Tomohiro Miyasaka
    Department of Neuropathology, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Tokyo 113 0033, Japan
    Neurobiol Dis 20:372-83. 2005
    ..Expression of GSK3 brought about slight deterioration in the touch response, while expression of HSP70 led to some improvement...
  96. pmc Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases
    Nicholas M Kanaan
    Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    J Neurosci 31:9858-68. 2011
    ..tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other ..
  97. ncbi Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain
    Koichi Wakabayashi
    Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
    Acta Neuropathol 120:1-12. 2010
    ..Further elucidation and characterization of PNS lesions will have implications for intravital biopsy diagnosis in neurodegenerative proteinopathy, particularly in Parkinson's disease...
  98. ncbi Identification of non-Alzheimer's disease tauopathies-related proteins by proteomic analysis
    Guofeng Yang
    Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing 100853, China
    Neurol Res 30:613-22. 2008
    To identify differentially expressed proteins between tauopathies cases and controls and to explore molecular mechanisms of tauopathies.
  99. pmc Detection of filamentous tau inclusions by the fluorescent Congo red derivative FSB [(trans,trans)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene]
    Ana Velasco
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    FEBS Lett 582:901-6. 2008
    ..More importantly, tau inclusions in the spinal cord of human P301S tau transgenic mice were labelled following a single intravenous injection of FSB. These findings indicate that FSB can be used to detect filamentous tau in vivo...
  100. ncbi 'Prion-like' propagation of mouse and human tau aggregates in an inducible mouse model of tauopathy
    Astrid Sydow
    Max Planck Unit for Structural Molecular Biology, Hamburg, Germany
    Neurodegener Dis 7:28-31. 2010
    ..However, since the mice contain both endogenous wild-type mouse tau and exogenous human mutant tau, the relative contribution of these components to the aggregates has been a matter of debate...
  101. ncbi Transgenic mouse model of tauopathies with glial pathology and nervous system degeneration
    Makoto Higuchi
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Neuron 35:433-46. 2002
    ..including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), are neurodegenerative tauopathies characterized by widespread CNS neuronal and glial tau pathologies, but there are no tau transgenic (Tg) mice ..

Research Grants72

  1. Mechanism of CD40 signaling to APP metabolism
    Michael J Mullan; Fiscal Year: 2013
    ..We have identified CD40 signaling as a potentially key modulator of both amyloid and tau pathology and this proposal seeks to identify downstream molecules which are more tractable from a drug development perspective. ..
  2. A Diarylheptanoid Scaffold to Treat Taopathies
    Chad A Dickey; Fiscal Year: 2013
    ..screen as a potent reducer of the structural protein tau, which accumulates in a group of diseases called the "tauopathies"...
  3. 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. ..
  4. A kinase pathway required for cortical neuron polarization
    Franck Polleux; Fiscal Year: 2012
    ..Recent evidence suggested that LKB1 disruption could participate to tauopathies such as Alzheimer's disease...
  5. TDP-43 acetylation as a pathogenic modification in ALS &related proteinopathies
    TODD JONATHAN COHEN; Fiscal Year: 2013
    ..that acetylation of the tau protein promotes tangle formation in Alzheimer's disease and related tauopathies (Nat Commun. 2011~2:252)...
  6. Mechanisms Underlying Tauopathy Following Traumatic Brain Injury
    David Brody; Fiscal Year: 2013
    ..The worldwide interest in athletes and military personnel with tau pathology and chronic traumatic encephalopathy underscores the urgency of this line of investigation. ..
  7. Identifying and characterizing gene(s) involved in beta-amyloid production.
    Huaxi Xu; Fiscal Year: 2013
    ..a major cause of AD, whereas hyperphosphorylated tau has been found in many neurodegenerative diseases known as tauopathies. Hence, identification of new genes/proteins involved in these processes is a major goal in AD research and may ..
  8. CLINICAL CORRELATES OF LONGITUDINAL PET CHANGES IN AD
    Mony J de Leon; Fiscal Year: 2013
    ..This project will test the hypothesis that validated biological markers for neurofibrillary tangle and amyloid plaque pathology contribute to FDG-PET in predicting future cognitive decline in cognitively normal subjects. ..
  9. Autophagic Clearance of Aberrant Tau: Biochemical and Therapeutic Implications
    Karen E Duff; Fiscal Year: 2013
    ..1 will examine the interplay between the UPS, AL-S and tau accumulation in human tissue from patients with 4R tauopathies and will compare to two mouse models of 4R tauopathy that have been modified to express an autophagic marker...
  10. Polyphenolic Interventions for tau Pathogenesis in Alzheimers Models
    SALLY ANN FRAUTSCHY; Fiscal Year: 2013
    ..Completion of aims will move the field forward in demonstrating interrelationship between tau aggregation, synapto/neuro-protection, inflammation, autophagy and the HSPs. ..
  11. Polarized transport in nervous system development and disease in zebrafish
    Philip Campbell; Fiscal Year: 2013
    ..NDs) represent a group of diseases including Alzheimer's disease, Parkinson's disease, and various tauopathies, characterized by similar phenotypic manifestations...
  12. MSUT2/SUT2 controls tau protein aggregation and neurotoxicity.
    Brian C Kraemer; Fiscal Year: 2013
    ..To better understand how abnormal tau contributes to neurodegeneration in AD and other tauopathies, we have established a model in C. elegans for tau aggregation and consequent neurodegeneration...
  13. Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors for
    ALAN D SNOW; Fiscal Year: 2011
    ..of tau aggregation/fibrillogenesis, and may have great potential as new therapeutic agents for AD and other tauopathies.] The major objective our proposal is to identify specific small molecule compounds from ProteoTech's ..
  14. Autoimmune biomarker profiling in tauopathy
    Irving E Vega; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Tauopathies are a family of neurodegenerative disorders characterized by the intracellular aggregation of filaments predominantly composed of hyperphosphorylated microtubule-associated protein tau...
  15. Tyrosine Phosphorylation in Alzheimer's Disease
    Gloria Lee; Fiscal Year: 2013
    ..Moreover, AD is now considered a "tauopathy". To discover new biomarkers and therapeutics for AD and other tauopathies, it is critical to determine how tau causes disease...
  16. Tau Nitration and Oxidation in Alzheimer's Disease
    LESTER IRVIN BINDER; Fiscal Year: 2010
    ..nitrated sites on tau to assess the timing and role of nitrative events during the course of AD and other tauopathies. We will also produce monoclonal antibodies to additional nitrated sites on tau and assess them in diseased ..
  17. Peripheral TGF-beta Pathway Inhibitor Therapy in Alzheimer's Rats
    Terrence Town; Fiscal Year: 2013
    ....
  18. Characterization of Small Molecule Splicing Modulators of MAPT and FGFR1
    Erik S Anderson; Fiscal Year: 2011
    ..b>Tauopathies, which are a set of neurodegenerative diseases characterized by altered splicing of microtubule associated ..
  19. A novel therapeutic approach to lowering tau and its impact on tauopathies
    NASSER HUSSEIN ZAWIA; Fiscal Year: 2013
    ..Neurofibrillary degeneration in the absence of [unreadable]- amyloid, is also seen in several tauopathies such as Guam parkinsonism dementia complex, dementia pugilistica, corticobasal degeneration, Pick's ..
  20. Pathogenic events triggered by tau acetylation in neurodegenerative tauopathy
    Tara Tracy; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Tauopathies are a class of age-related neurodegenerative diseases that millions of people in our country suffer from today...
  21. Canonical Wnt Signaling by the Proteolytc Processing of LRP6
    BRANDON RICHARD BEAGLE; Fiscal Year: 2010
    ..and has been implicated in generating aberrantly hyperphosporylated tau proteins associated with AD and other tauopathies. Hence, identifying the mechanisms and proteins that regulate GSK3 activity will provide pertinent pathological ..
  22. ROLE OF HSP 110 IN TAUOPATHY
    Nahid F Mivechi; Fiscal Year: 2013
    ..The neuropathological hallmarks of AD and other tauopathies include accumulation of senile plaques and/or neurofibrillary tangles (NFTs) that causes neurons to degenerate...
  23. Mouse Models with Regulatable Cell Type-specific Expression of Anti-Tau shRNAs
    Lennart Mucke; Fiscal Year: 2012
    ..in Alzheimer's disease (AD) and a variety of other neurological conditions collectively referred to as tauopathies. Remarkably, the functions tau fulfills in the adult brain and the exact roles it plays in the pathogenesis of ..
  24. The unfolded protein response and neurodegenerative tauopathies
    Lauren D Stutzbach; Fiscal Year: 2013
    ..Aim 3 will make use of human lymphoblastoid cell lines to determine how protein coding changes in the PERK protein affect its function as part of the UPR. ..
  25. Tau Protein Aggregation Inhibitors for Tauopathies
    ALAN D SNOW; Fiscal Year: 2013
    ..aromatic compounds can also serve as direct inhibitors of tau aggregation/fibrillogenesis in mouse models of tauopathies. These compounds are believed to possess great potential as new therapeutic agents for AD and related ..
  26. Frontal Lobe Neuroimaging as a Biomarker of Chronic Traumatic Encephalopathy
    JULIE MARIE STAMM; Fiscal Year: 2012
    ..This study is part of a larger study, which is the first to address these issues and, therefore, may have a considerable impact on public health. ..
  27. The role of fractalkine signaling in neurodegenerative disease
    Richard M Ransohoff; Fiscal Year: 2013
    ..Similarly in non-AD tauopathies, there is both abundant MAPT pathology and neuroinflammation...
  28. Development of Zebrafish Taupoathy Models for Translational Research
    EDWARD ALAN BURTON; Fiscal Year: 2013
    ..be a valuable tool for translational studies to develop new therapies for PSP and CBD, and potentially other Tauopathies such as Alzheimer's disease and chronic head injury...
  29. Chemical Probes and Chaperone-Accelerated Turnover of Tau
    Jason E Gestwicki; Fiscal Year: 2013
    ..Thus, strategies for accelerating the removal of abnormal tau are expected to protect against tauopathies. Cellular protein quality control (PQC) pathways, including molecular chaperones, have been shown to regulate ..
  30. The role of a novel tau-associated protein in neurodegeneration
    Irving E Vega; Fiscal Year: 2012
    b>Tauopathies are a family of neurodegenerative disorders characterized by the intracellular aggregation of filaments derived from hyperphosphorylated microtubule-associated protein tau...
  31. Alzhelmer's Disease Drug Development Program
    Amos B Smith; Fiscal Year: 2012
    ..system (CMS) are sequestered into filamentous inclusions that are the signature lesions of AD and related tauopathies, thereby compromising the normal function of tau in stabilizing and maintaining MT networks essential for ..
  32. The role of microglial-and neuron-specific MyD88 signaling in tauopathies
    Kiran Bhaskar; Fiscal Year: 2013
    ..of microtubule-associated protein tau (MAPT) and neurodegeneration are hallmarks of many neurodegenerative tauopathies. Although, the exact etiology of many of these tauopathies remains elusive, neuropathologically, they are ..
  33. Chronic Traumatic Encephalopathy: Clinical Presentation and Biomarkers
    Robert A Stern; Fiscal Year: 2013
    ..abstract_text> ..
  34. Epitope-Specific Targeting of Tau Aggregates.
    Einar M Sigurdsson; Fiscal Year: 2013
    ..tau protein has recently become attractive as a potential therapy for Alzheimer's disease (AD) and related tauopathies. We previously showed that active immunization targeting a disease-related phospho-tau epitope reduces cerebral ..
  35. Genetic and Environmental Risk Factors for PSP
    Irene Litvan; Fiscal Year: 2010
    ..Understanding the etiology of PSP may also help explain the causes of other tauopathies such as Alzheimer's disease...
  36. Parkin protection in gene transfer animal models (KO-1 Award)
    Charbel Moussa; Fiscal Year: 2012
    ..an important pathological landmark in Parkinson's disease [PD], Alzheimer's disease [AD] and the tauopathies with Parkinsonism...
  37. PTEN, Cell Cycle and Neurofibrillary Degeneration
    Francesca Fang Liao; Fiscal Year: 2012
    ..Although NFTs are coincident with cell death in several neurodegenerative diseases, known as tauopathies, and most notably in AD, the molecular mechanisms leading to this chronic loss of neuronal cells is still not ..
  38. The Hsp90 cochaperone FKBP51 regulates tau structure and function
    Chad A Dickey; Fiscal Year: 2013
    ..tau and whether it is a rational therapeutic target for treating AD, Parkinson's disease (PD), and other tauopathies. Tau aggregation is a central component of Alzheimer's disease (AD) and ~15 other neurodegenerative ..
  39. Endosomal-Lysosomal Function in Neuronal Storage Disease
    STEVEN UPSHAW WALKLEY; Fiscal Year: 2013
    ....
  40. The Role of Monocytes and Microglia in Traumatic Brain Injury-Induced Tauopathies
    Richard M Ransohoff; Fiscal Year: 2013
    ..exposed to TBI are at a greatly increased risk for developing a number of neurodegenerative diseases termed tauopathies, including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE)...
  41. Clearance and In Vivo Detection of Tau Pathology
    Einar M Sigurdsson; Fiscal Year: 2013
    ..Obviously, tau pathology is another important target in AD, and the primary one in other tauopathies. Presence of pathological tau correlates much better with the degree of dementia than A[unreadable] deposition...
  42. Gene discovery in PSP by transcriptome, neuropathology and sequence analysis
    Nilufer Ertekin-Taner; Fiscal Year: 2013
    ..Given the clinicopathological overlap between PSP and other tauopathies, our proposal is expected to impact a wide range of neurodegenerative disorders and generate novel therapeutic ..
  43. Pharmacological modulation of tau neurotoxicity in vivo
    Mel B Feany; Fiscal Year: 2012
    ..We now propose using our model of Alzheimer's disease and related tauopathies to identify drugs that can ameliorate neurotoxicity in vivo...
  44. INVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASE
    JOEL SYNES PERLMUTTER; Fiscal Year: 2013
    ..These steps are critical for development of effective treatment of dementia associated with PD. ..
  45. GENETICS AND MOLECULAR BIOLOGY OF PARKINSONISM
    DENNIS WILLIAM DICKSON; Fiscal Year: 2013
    ..tau is related PD and how tau-directed therapies may translate into novel treatments for PD and parkinsonian tauopathies. The proposed Center will have three projects and four cores with an overarching theme to understand the role ..
  46. 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 ..
  47. Role of Tau Cleavage in Tauopathy
    Karen H Ashe; Fiscal Year: 2013
    This project aims to validate a novel drug target for tauopathies [unreadable] a group of incurable neurodegenerative conditions that includes Alzheimer[unreadable]s disease (AD)...
  48. Tau-mediated chromatin regulation and neurodegeneration
    SUSAN E FROST; Fiscal Year: 2012
    ..the most frequent form of dementia, and over twenty other neurodegenerative diseases, collectively termed "tauopathies." There is currently no disease-modifying treatment available for AD or other tauopathies...
  49. High-Throughput Nanoscale Approaches to Studying and Inhibiting Amyloid Toxicity
    Timothy Lu; Fiscal Year: 2011
    ..this system can be applied to discover peptide inhibitors of other diseases, such as viral infections and tauopathies. This high-throughput platform is enabled by our expertise in synthetic biology and bacterial engineering...
  50. 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. ..
  51. Kinases Linking Abeta and Tau to Synaptic Dysfunction
    Lennart Mucke; Fiscal Year: 2013
    ..frontotemporal lobar degeneration (FTLD) and a variety of other neurodegenerative conditions referred to as "tauopathies." Preliminary data obtained during the preceding funding period suggest that neuronal and behavioral ..
  52. Tracking the Propagation of Misfolded Tau: A Study of Cellular Uptake and Traffic
    BRANDON BLAKE HOLMES; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Tauopathies are a class of neurodegenerative disorders characterized by the pathological accumulation of microtubule-associated protein tau in the human brain...
  53. Prolyl Isomerase Pin 1 and Neurodegeneration
    Kun Ping Lu; Fiscal Year: 2009
    ..assembly, little is known about what phosphorylation actually does and how it affects the pathogenesis of the tauopathies. Interestingly, pSer/Thr- Pro motifs in proteins exist in distinct cis and trans conformations, whose ..
  54. High throughput tau oligomer drug screening assay for Alzheimer's disease
    James G Moe; Fiscal Year: 2013
    ..least three or more lead candidate compounds targeting tau oligomers for evaluation in animal models of AD and tauopathies. To attain this result, secondary screening in cell models of tau oligomer formation and medicinal chemistry ..
  55. A Mouse Model of Tau Pathology in AD and Other Dementias
    PETER P DAVIES; Fiscal Year: 2013
    ..efficacy raises many questions that will need to be addressed before this approach can be tested in humans with tauopathies, not the least of which is the nature of the antibody required for efficacy...
  56. Biological and Pathological Interactions between Tau and LRRK2
    JADA M LEWIS; Fiscal Year: 2013
    ..be disrupted as it becomes hyperphosphorylated and aggregated in a family of neurodegenerative diseases termed tauopathies. Tau mutation is causative for the tauopathy frontotemporal dementia and parkinsonism linked to chromosome 17 (..
  57. Elucidating the Pathology of Impact-Induced Traumatic Brain Injury
    CHAD ALAN TAGGE; Fiscal Year: 2013
    ..Insight gained from this work will also facilitate development of urgently needed diagnostics and therapeutics for these devastating disorders. ..
  58. Molecular determinants of lamin a accumulation in human aging and disease
    Agnieszka Kalinowski; Fiscal Year: 2012
    ..other pathologies that result from destructive protein-membrane interactions, such as Alzheimer's disease, tauopathies and prion diseases...
  59. Inhibition of Hsp70 ATPase activity reduces tau through the cellular degradation
    JOHN CLARENCE O'LEARY; Fiscal Year: 2013
    ..the microtubule associated protein tau, abnormally aggregates in numerous neurodegenerative diseases termed tauopathies. Some chaperone proteins have shown auspicious results as therapeutic targets in models of tauopathy...
  60. CELL-CELL TRANSFER AND PROPAGATION OF TAU AGGREGATES
    Marc I Diamond; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cell-cell transfer and propagation of tau aggregates. Tauopathies are devastating neurodegenerative diseases...
  61. Phosphoprotein phosphatase 2A, a new target for Alzheimer's Disease interventio
    STEVEN BRAITHWAITE; Fiscal Year: 2010
    ..Abnormal hyperphosphorylation of tau plays an important role in Alzheimer's disease (AD) and other tauopathies. Current therapeutic approaches with focus on tau kinases (e.g...
  62. Genetic Determinants of Tauopathies
    Jason Chen; Fiscal Year: 2013
    ..are still unclear, variants in the MAPT gene, encoding for tau, have been identified as causal in some tauopathies, and the H1 haplotype at the 17q21...
  63. Colloquium on the Cytoskeleton and Human Disease
    Leslie Wilson; Fiscal Year: 2001
    ..new compounds), 2)microtubule-associated proteins and neurodegenerative disease (Alzheimer's disease and other tauopathies, new concepts and new targets), 3)intermediate filaments and disease (keratin and skin diseases, desmin in ..
  64. BIOLOGY OF CHROMOSOME 17 LINKED DEMENTIA WITH TAUOPATHY
    Jill Murrell; Fiscal Year: 2000
    ..The members of the team are highly experienced investigators in their field of endeavor. ..
  65. Tau phosphorylation and neurodegeneration
    Alejandra del C Alonso; Fiscal Year: 2009
    ..in vitro results and of different tau phosphorylation sites will provide an explanation of the progression of tauopathies and it will identify new therapeutic targets for neurodegenerative diseases...
  66. Modeling Human Tauopathies in Drosophila melanogaster
    Gena Heidary; Fiscal Year: 2003
    ..melanogaster to determine the role of the microtubule-associated protein (MAP) tau in the pathogenesis of human tauopathies. The tau protein has been implicated in at least 20 neurodegenerative diseases collectively referred to as ..
  67. MECHANISM AND CONTROL OF BRAIN MICROTUBULE DYNAMICS
    Leslie Wilson; Fiscal Year: 2009
    ..how the tau proteins, which stabilize microtubules and may mis-regulate dynamics in neurodegenerative tauopathies such as Frontotemporal Dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and the stathmin/SCG10 ..
  68. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2006
    ..the hypothesis that their disruption promotes the accumulation of hyperphosphorylated forms of tau in all tauopathies. The first aim will focus on establishing major properties of PP2A/tau and PP2A/MT interactions in vitro and in ..
  69. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2007
    ..PP2A in human brain regions during normal aging, and assess whether it becomes altered in AD and other tauopathies. If our model is validated, dietary folate supplementation and PPMT may be novel therapeutic targets for ..
  70. Biology of Tauopathies Studied with HSV Amplicons
    E Antonio Chiocca; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  71. Genetic Analysis of Tau H1 in Parkinsonism
    Matthew Farrer; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): The tau H1 association in 4R tauopathies, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), is fundamental to their etiology, yet the underlying mutation(s) and ..
  72. Development of Radiopharmaceuticals for Imaging Brain Tau Pathology
    Daniel Skovronsky; Fiscal Year: 2009
    ..of Alzheimer's disease and for 2) Improving early and accurate diagnosis of Alzheimer's and related tauopathies. To test this hypothesis, we will screen for and develop a novel 18F-labeled radiopharmaceutical to ..