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. Kara E, Ling H, Pittman A, Shaw K, de Silva R, Simone R, et al. The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features. Neurobiol Aging. 2012;33:2231.e7-2231.e14 pubmed publisher
    ..tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p...
  2. Ramachandran G, Udgaonkar J. Mechanistic studies unravel the complexity inherent in tau aggregation leading to Alzheimer's disease and the tauopathies. Biochemistry. 2013;52:4107-26 pubmed publisher
    ..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...
  3. Kovacs G, Wohrer A, Strobel T, Botond G, Attems J, Budka H. Unclassifiable tauopathy associated with an A152T variation in MAPT exon 7. Clin Neuropathol. 2011;30:3-10 pubmed
    ..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...
  4. Badiola N, Suarez Calvet M, Lleo A. Tau phosphorylation and aggregation as a therapeutic target in tauopathies. CNS Neurol Disord Drug Targets. 2010;9:727-40 pubmed
    b>Tauopathies are neurodegenerative diseases characterized by insoluble hyperphosphorylated deposits of the microtubule-associated protein tau in the central nervous system...
  5. Dickson D, Kouri N, Murray M, Josephs K. Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J Mol Neurosci. 2011;45:384-9 pubmed publisher
    ..Even FTLD-tau determined by MAPT mutations has clinical and pathologic heterogeneity. Tauopathies are subclassified according to the predominant species of tau that accumulates, with respect to alternative ..
  6. Khurana V, Merlo P, DUBOFF B, Fulga T, Sharp K, Campbell S, et al. A neuroprotective role for the DNA damage checkpoint in tauopathy. Aging Cell. 2012;11:360-2 pubmed publisher
    ..Surprisingly, checkpoint attenuation potently increases neurodegeneration through aberrant cell cycle re-entry of postmitotic neurons. These data suggest an unexpected neuroprotective role for the DNA damage checkpoint in tauopathies.
  7. Paquet D, Schmid B, Haass C. Transgenic zebrafish as a novel animal model to study tauopathies and other neurodegenerative disorders in vivo. Neurodegener Dis. 2010;7:99-102 pubmed publisher
    Our ageing society is confronted with a dramatic increase in patients suffering from tauopathies such as Alzheimer's disease, frontotemporal dementia and others...
  8. McKee A, Stern R, Nowinski C, Stein T, Alvarez V, Daneshvar D, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136:43-64 pubmed publisher
  9. Grinberg L, Wang X, Wang C, Sohn P, Theofilas P, Sidhu M, et al. Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation. Acta Neuropathol. 2013;125:581-93 pubmed publisher
    ..Recent studies have shown co-localization of acetylated and phosphorylated tau in AD and some 4R tauopathies. We developed a novel monoclonal antibody against acetylated tau at lysine residue 274, which recognizes both ..

Scientific Experts

More Information

Publications62

  1. Yamada K, Holth J, Liao F, Stewart F, Mahan T, Jiang H, et al. Neuronal activity regulates extracellular tau in vivo. J Exp Med. 2014;211:387-93 pubmed publisher
    ..The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself...
  2. Niblock M, Gallo J. Tau alternative splicing in familial and sporadic tauopathies. Biochem Soc Trans. 2012;40:677-80 pubmed publisher
    ..Tau alternative splicing could represent a target for therapeutic intervention to delay the progression of pathology in familial as well as sporadic tauopathies.
  3. Trabzuni D, Wray S, Vandrovcova J, Ramasamy A, Walker R, Smith C, et al. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies. Hum Mol Genet. 2012;21:4094-103 pubmed publisher
  4. Schulz K, Eckert A, Rhein V, Mai S, Haase W, Reichert A, et al. A new link to mitochondrial impairment in tauopathies. Mol Neurobiol. 2012;46:205-16 pubmed publisher
    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...
  5. Lasagna Reeves C, Castillo Carranza D, Jackson G, Kayed R. Tau oligomers as potential targets for immunotherapy for Alzheimer's disease and tauopathies. Curr Alzheimer Res. 2011;8:659-65 pubmed
    ..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 A? toxicity in AD; specifically, aggregates of a size intermediate between monomers ..
  6. Liu L, Drouet V, Wu J, Witter M, Small S, CLELLAND C, et al. Trans-synaptic spread of tau pathology in vivo. PLoS ONE. 2012;7:e31302 pubmed publisher
    ..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...
  7. Kopeikina K, Polydoro M, Tai H, Yaeger E, Carlson G, Pitstick R, et al. Synaptic alterations in the rTg4510 mouse model of tauopathy. J Comp Neurol. 2013;521:1334-53 pubmed publisher
    ..Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model...
  8. Fox L, William C, Adamowicz D, Pitstick R, Carlson G, Spires Jones T, et al. Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model. J Neuropathol Exp Neurol. 2011;70:588-95 pubmed publisher
    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 ..
  9. Ferreira A, Bigio E. Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathies. Mol Med. 2011;17:676-85 pubmed publisher
    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 ..
  10. Ballatore C, Brunden K, Trojanowski J, Lee V, Smith A, Huryn D. Modulation of protein-protein interactions as a therapeutic strategy for the treatment of neurodegenerative tauopathies. Curr Top Med Chem. 2011;11:317-30 pubmed
    ..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 ..
  11. Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M. "Prion-like" templated misfolding in tauopathies. Brain Pathol. 2013;23:342-9 pubmed publisher
    ..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 ..
  12. Brunden K, Zhang B, Carroll J, Yao Y, Potuzak J, Hogan A, et al. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010;30:13861-6 pubmed publisher
    ..Accordingly, a possible therapeutic strategy for AD and related "tauopathies" is treatment with a MT-stabilizing anti-cancer drug such as paclitaxel...
  13. Hampton D, Webber D, Bilican B, Goedert M, Spillantini M, Chandran S. Cell-mediated neuroprotection in a mouse model of human tauopathy. J Neurosci. 2010;30:9973-83 pubmed publisher
    ..Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau...
  14. Rodriguez Navarro J, Rodriguez L, Casarejos M, Solano R, Gomez A, Perucho J, et al. Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiol Dis. 2010;39:423-38 pubmed publisher
    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...
  15. Ludvigson A, Luebke J, Lewis J, Peters A. Structural abnormalities in the cortex of the rTg4510 mouse model of tauopathy: a light and electron microscopy study. Brain Struct Funct. 2011;216:31-42 pubmed publisher
    ..However, no glial cells are seen to contain tau in their cytoplasm. These observations add to the base of knowledge available on this commonly employed model of tauopathy...
  16. Schaeffer V, Lavenir I, Ozcelik S, Tolnay M, Winkler D, Goedert M. Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain. 2012;135:2169-77 pubmed publisher
    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 ..
  17. Scattoni M, Gasparini L, Alleva E, Goedert M, Calamandrei G, Spillantini M. Early behavioural markers of disease in P301S tau transgenic mice. Behav Brain Res. 2010;208:250-7 pubmed publisher
    ..Mice transgenic for human P301S tau protein exhibit many characteristics of human tauopathies, including neurodegeneration, the formation of neuronal tau inclusions in the brain and the development of a ..
  18. Van der Jeugd A, Hochgräfe K, Ahmed T, Decker J, Sydow A, Hofmann A, et al. Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau. Acta Neuropathol. 2012;123:787-805 pubmed publisher
    ..It offers potential to evaluate drugs with regard to learning and memory performance. ..
  19. Lee G, Leugers C. Tau and tauopathies. Prog Mol Biol Transl Sci. 2012;107:263-93 pubmed publisher
    b>Tauopathies are age-related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau...
  20. Iijima Ando K, Iijima K. Transgenic Drosophila models of Alzheimer's disease and tauopathies. Brain Struct Funct. 2010;214:245-62 pubmed publisher
    ..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 ..
  21. Brunden K, Ballatore C, Crowe A, Smith A, Lee V, Trojanowski J. Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors. Exp Neurol. 2010;223:304-10 pubmed publisher
    ..as there are an increasing number of research programs that are exploring ways to reduce NFTs in AD and related tauopathies. We briefly review recent advances in tau-based drug discovery, with an emphasis on the identification of ..
  22. Nijholt D, van Haastert E, Rozemuller A, Scheper W, Hoozemans J. The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies. J Pathol. 2012;226:693-702 pubmed publisher
    ..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 ..
  23. Wilhelmus M, de Jager M, Rozemuller A, Brevé J, Bol J, Eckert R, et al. Transglutaminase 1 and its regulator tazarotene-induced gene 3 localize to neuronal tau inclusions in tauopathies. J Pathol. 2012;226:132-42 pubmed publisher
    ..dementia and parkinsonism linked to chromosome 17 (FTDP-17), and Pick's disease (PiD) are commonly known as tauopathies. Neurodegeneration observed in these diseases is linked to neuronal fibrillary hyperphosphorylated tau protein ..
  24. Menuet C, Borghgraef P, Matarazzo V, Gielis L, Lajard A, Voituron N, et al. Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: possible implications for tauopathies and Alzheimer's disease. Respir Physiol Neurobiol. 2011;178:290-303 pubmed publisher
    b>Tauopathies, including Alzheimer's disease are the most frequent neurodegenerative disorders in elderly people...
  25. Krinke D, Jahnke H, Mack T, Hirche A, Striggow F, Robitzki A. A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoring. Biosens Bioelectron. 2010;26:162-8 pubmed publisher
    ..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...
  26. Talmat Amar Y, Arribat Y, Redt Clouet C, Feuillette S, Bouge A, Lecourtois M, et al. Important neuronal toxicity of microtubule-bound Tau in vivo in Drosophila. Hum Mol Genet. 2011;20:3738-45 pubmed publisher
    ..Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease...
  27. Constantinescu R, Andreasson U, Holmberg B, Zetterberg H. Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathies. Acta Neurol Scand. 2013;127:e8-12 pubmed publisher
    ..Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA)...
  28. Haggerty T, Credle J, Rodriguez O, Wills J, Oaks A, Masliah E, et al. Hyperphosphorylated Tau in an ?-synuclein-overexpressing transgenic model of Parkinson's disease. Eur J Neurosci. 2011;33:1598-610 pubmed publisher
    Although clinically distinct diseases, tauopathies and synucleinopathies share a common genesis and mechanisms, leading to overlapping degenerative changes within neurons...
  29. DUBOFF B, Götz J, Feany M. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron. 2012;75:618-32 pubmed publisher
    ..Our results thus identify actin-mediated disruption of mitochondrial dynamics as a direct mechanism of tau toxicity in neurons in vivo...
  30. Ballatore C, Brunden K, Huryn D, Trojanowski J, Lee V, Smith A. Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies. J Med Chem. 2012;55:8979-96 pubmed publisher
    ..that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-..
  31. Kimura T, Whitcomb D, Jo J, Regan P, Piers T, Heo S, et al. Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philos Trans R Soc Lond B Biol Sci. 2014;369:20130144 pubmed publisher
    ..of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is ..
  32. Ohmi K, Kudo L, Ryazantsev S, Zhao H, Karsten S, Neufeld E. Sanfilippo syndrome type B, a lysosomal storage disease, is also a tauopathy. Proc Natl Acad Sci U S A. 2009;106:8332-7 pubmed publisher
    ..gyrus neurons showed cytoplasmic inclusions of paired helical filaments, P-tau aggregates characteristic of tauopathies-a group of age-related dementias that include Alzheimer disease...
  33. Van der Jeugd A, Ahmed T, Burnouf S, Belarbi K, Hamdame M, Grosjean M, et al. Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. Neurobiol Learn Mem. 2011;95:296-304 pubmed publisher
  34. Cowan C, Chee F, Shepherd D, Mudher A. Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy. Biochem Soc Trans. 2010;38:564-70 pubmed publisher
    ..This leads to synaptic dysfunction. We have tested this theory in a Drosophila model of tauopathies in which we expressed human tau (h-tau)...
  35. Hall G, Patuto B. Is tau ready for admission to the prion club?. Prion. 2012;6:223-33 pubmed publisher
  36. de Calignon A, Polydoro M, Suarez Calvet M, William C, Adamowicz D, Kopeikina K, et al. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron. 2012;73:685-97 pubmed publisher
    ..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 of tau-induced neurodegeneration...
  37. Wakabayashi K, Mori F, Tanji K, Orimo S, Takahashi H. Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol. 2010;120:1-12 pubmed publisher
    ..Further elucidation and characterization of PNS lesions will have implications for intravital biopsy diagnosis in neurodegenerative proteinopathy, particularly in Parkinson's disease...
  38. Spillantini M, Goedert M. Tau pathology and neurodegeneration. Lancet Neurol. 2013;12:609-22 pubmed publisher
    ..filamentous tau protein is at the centre of many human neurodegenerative diseases, collectively referred to as tauopathies. Dominantly inherited mutations in MAPT, the gene that encodes tau, cause forms of frontotemporal dementia and ..
  39. Höglinger G, Melhem N, Dickson D, Sleiman P, Wang L, Klei L, et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet. 2011;43:699-705 pubmed publisher
    ..Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease...
  40. Yanamandra K, Kfoury N, Jiang H, Mahan T, Ma S, Maloney S, et al. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron. 2013;80:402-414 pubmed publisher
    ..occurs in neurodegenerative diseases including Alzheimer's disease and many other disorders collectively termed tauopathies. trans-cellular propagation of tau pathology, mediated by extracellular tau aggregates, may underlie ..
  41. Shiryaev N, Pikman R, Giladi E, Gozes I. Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspects. Curr Pharm Des. 2011;17:2603-12 pubmed
    ..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...
  42. Prusiner S. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet. 2013;47:601-23 pubmed publisher
    ..NDs), including Alzheimer's, Parkinson's, Creutzfeldt-Jakob, and Lou Gehrig's diseases, as well as the tauopathies. The majority of NDs are sporadic, and 10% to 20% are inherited...
  43. Mellone M, Kestoras D, Andrews M, Dassie E, Crowther R, Stokin G, et al. Tau pathology is present in vivo and develops in vitro in sensory neurons from human P301S tau transgenic mice: a system for screening drugs against tauopathies. J Neurosci. 2013;33:18175-89 pubmed publisher
    ..P301S-htau-positive neurons grew aberrant axons, including spheroids, typically found in human tauopathies. Neurons cultured at advanced stages of tau pathology showed a 60% decrease in the fraction of moving ..
  44. Sanders D, Kaufman S, DeVos S, Sharma A, Mirbaha H, Li A, et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron. 2014;82:1271-88 pubmed publisher
    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 ..
  45. Caccamo A, Magrí A, Medina D, Wisely E, López Aranda M, Silva A, et al. mTOR regulates tau phosphorylation and degradation: implications for Alzheimer's disease and other tauopathies. Aging Cell. 2013;12:370-80 pubmed publisher
    Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia...
  46. Boimel M, Grigoriadis N, Lourbopoulos A, Touloumi O, Rosenmann D, Abramsky O, et al. Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathy. J Neuropathol Exp Neurol. 2009;68:314-25 pubmed publisher
    ..Statins may provide therapy against NFTs in tauopathies, particularly when NFTs are the major neuropathologic component.
  47. Sudo H, Baas P. Strategies for diminishing katanin-based loss of microtubules in tauopathic neurodegenerative diseases. Hum Mol Genet. 2011;20:763-78 pubmed publisher
    It is commonly stated that microtubules gradually disintegrate as tau becomes dissociated from them in tauopathies such as Alzheimer's disease...
  48. Min S, Cho S, Zhou Y, Schroeder S, Haroutunian V, Seeley W, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron. 2010;67:953-66 pubmed publisher
    Neurodegenerative tauopathies characterized by hyperphosphorylated tau include frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD)...
  49. Iqbal K, Liu F, Gong C, Grundke Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res. 2010;7:656-64 pubmed
    ..Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
  50. Polydoro M, Acker C, Duff K, Castillo P, Davies P. Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci. 2009;29:10741-9 pubmed publisher
    ..Our results suggest that tau pathology may underlie an age-dependent learning impairment through disruption of synaptic function...
  51. Rocher A, Crimins J, Amatrudo J, Kinson M, Todd Brown M, Lewis J, et al. Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp Neurol. 2010;223:385-93 pubmed publisher
    ..tangles (NFTs), neuronal death, and memory impairment, reminiscent of the pathology observed in human tauopathies. In the present study, we examined the effects of mutant tau expression on the electrophysiology and morphology ..
  52. Duyckaerts C, Delatour B, Potier M. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. 2009;118:5-36 pubmed publisher
  53. Hanger D, Anderton B, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med. 2009;15:112-9 pubmed publisher
    ..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...