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Tauopathies and α-Synucleinopathies

  • Conference paper
Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders

Part of the book series: Research and Perspectives in Alzheimer’s Disease ((ALZHEIMER))

Abstract

Alzheimer’s disease and Parkinson’s disease are the most common neurodegenerative diseases of the human brain. They are characterized by the presence of ordered filamentous assemblies that gradually develop in a small number of types of nerve cell. In Alzheimer’s disease, vulnerable nerve cells develop neurofibrillary tangles, neuropil threads and abnormal neurites, whereas in Parkinson’s disease they develop Lewy bodies and Lewy neurites (Goedert et al. 1998a). Alzheimer’s disease is characterized by the additional presence of extracellular deposits in the form of amyloid plaques. Over recent years, it has become clear that intraneuronal filamentous deposits of Alzheimer’s disease and Parkinson’s disease are composed of tau protein and α-synuclein, respectively. Filamentous tau protein deposits are also the defining neuropathological hallmark of a number of other dementing or movement disorders, such as Pick’s disease, progressive supranuclear palsy, corticobasal degeneration and the group of familial fron-totemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Filamentous α-synuclein deposits in cerebral cortex define dementia with Lewy bodies, a common late-life dementia that exists in a pure form or overlaps with the neuropathological changes of Alzheimer’s disease. Moreover, multiple system atrophy has been shown to be a third α-synucleinopathy.

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References

  • Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M (1998) NACP/a-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy. Acta Neuropathol 96:439–444

    Article  PubMed  CAS  Google Scholar 

  • Arrasate M, Perez M, Armas-Portela R, Avila J (1999) Polymerization of tau peptides into fibrillar structures. The effect of FTDP-17 mutations. FEBS Lett 446:199–202

    Article  PubMed  CAS  Google Scholar 

  • Baba M, Nakajo S, Tu P-H, Tomita T, Nakaya K, Lee VM-Y, Trojanowski JQ, Iwatsubo T (1998) Aggregation of a-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 152:879–884

    PubMed  CAS  Google Scholar 

  • Bird TD, Nochlin D, Poorkaj P, Cherrier M, Kaye J, Payami H, Peskind E, Lampe TH, Nemens E, Boyer PJ, Schellenberg GD (1999) A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 122:741–756

    Article  PubMed  Google Scholar 

  • Bramble« GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM-Y (1993) Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding. Neuron 19:1089–1099

    Article  Google Scholar 

  • Bugiani O, Murrell JR, Giaccone G, Hasegawa M, Ghigo G, Tabaton M, Morbin M, Primavera A, Carella F, Solaro C, Grisoli M, Savoiardo M, Spillantini MG, Tagliavini F, Goedert M, Ghetti B (1999) Fronto-temporal dementia and corticobasal degeneration in a family with a P301S mutation in Tau. J Neuro-pathol Exp Neurol 58:667–677

    Article  CAS  Google Scholar 

  • Clark LN, Poorkaj P, Wszolek Z, Geschwind DH, Nasreddine ZS, Miller B, LI D, Payami H, Awert F, Markopoulou K, Andreadis A, D’Souza I, Lee VM-Y, Reed L, Trojanowski JQ, Zhukareva V, Bird T, Schellenberg G, Wilhelmsen KC (1998) Pathogenic implications of mutations in the tau gene in pallido-ponto-nigral degeneration and related neurodegenerative disorders linked to chromosome 17. Proc Natl Acad Sci USA 95:13103–13107

    Article  PubMed  CAS  Google Scholar 

  • Conway KA, Harper JD, Lansbury PT (1998) Accelerated in vitro fibril formation by a mutant a-synuclein linked to early-onset Parkinson disease. Nature Med 4:1318–1320

    Article  PubMed  CAS  Google Scholar 

  • Crowther RA (1991) Structural aspects of pathology in Alzheimer’s disease. Biochim Biophys Acta 1069:1–9

    Article  Google Scholar 

  • Crowther RA, Jakes R, Spillantini MG, Goedert M (1999) Synthetic filaments assembled from C-terminally truncated a-synuclein. FEBS Lett 436:309–312

    Article  Google Scholar 

  • Davidson WS, Jonas A, Clayton DF, George JM (1998) Stabilization of a-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem 273:9443–9449

    Article  PubMed  CAS  Google Scholar 

  • Delacourte A, Sergeant N, Wattez A, Gauvreau D, Robitaille Y (1998) Vulnerable neuronal subsets in Alzheimer’s and Pick’s disease are distinguished by their tau isoform distribution and phosphorylation. Ann Neurol 43:193–204

    Article  PubMed  CAS  Google Scholar 

  • D’Souza I, Poorkaj P, Hong M, Nochlin D, Lee VM-Y, Bird T, Schellenberg GD (1999) Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Natl Acad Sci USA 96:5598–5603

    Article  PubMed  Google Scholar 

  • Dumanchin C, Camuzat A, Campion D, Verpillat P, Hannequin D, Dubois B, Saugier-Veber P, Martin C, Penet C, Charbonnier F, Agid Y, Frebourg T, Brice A (1998) Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum Mol Genet 7:1825–1829

    Article  PubMed  CAS  Google Scholar 

  • Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272

    Article  PubMed  CAS  Google Scholar 

  • Foster NL, Wilhelmsen KC, Sima AAF, Jones MZ, D’Amato C, Gilman S, Spillantini MG, Lynch T, Mayeux RP, Gaskell PC, Hulette C, Pericak-Vance MA, Welsh-Bohmer KA, Dickson DW, Heutink P, Kros J, Van Swieten JC, Arwert F, Ghetti B, Murrell J, Lannfelt L, Hutton M, Phelps CH, Snyder DS, Oliver E, Ball MJ, Cummings JL, Miller BL, Katzman R, Reed L, Schelper RL, Lanska DJ, Brun A, Fink JK, Khul DE, Knopman DS, Wszolek Z, Miller CL, Bird TD, Lendon C, Elechi C (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: A consensus statement. Ann Neurol 41:706–715

    Article  PubMed  CAS  Google Scholar 

  • Gai WP, Power JHT, Blumbergs PC, Blessing WW (1998) Multiple system atrophy: a new a-synuclein disease? Lancet 352:547–548

    Article  PubMed  CAS  Google Scholar 

  • Giasson BI, Uryu K, Trojanowski JQ, Lee VM-Y (1999) Mutant and wild type human a-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 274:7619–7622

    Article  PubMed  CAS  Google Scholar 

  • Ginsberg SD, Crino PB, Lee VM-Y, Eberwine JH, Trojanowski JQ (1997) Sequestration of RNA in Alzheimer’s disease neurofibrillary tangles and senile plaques. Ann Neurol 41:200–209

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA (1989) Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3:519–526

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Crowther RA (1992a) Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system. Proc Natl Acad Sci USA 89:1983–1987

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Cairns NJ, Crowther RA (1992b) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8:159–168

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith M J, Crowther RA (1996) Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosami-noglycans. Nature 383:550–553

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P (1997) Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases. FEBS Lett 409:57–62

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Davies SW (1998a) Filamentous nerve cell inclusions in neurodegenerative diseases. Curr Opin Neurobiol 8:619–632

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Crowther RA, Spillantini MG (1998b) Tau mutations cause frontotemporal dementias. Neuron 21:955–958

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Spillantini MG, Crowther RA, Chen SG, Parchi P, Tabaton M, Lanska DJ, Markesbery WR, Wilhelmsen KC, Dickson DW, Petersen RB, Gambetti P (1999a) Tau gene mutation in familial progressive subcortical gliosis. Nature Med 5:454–457

    Article  PubMed  CAS  Google Scholar 

  • Goedert M, Jakes R, Crowther RA (1999b) Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett 450:306–311

    Article  PubMed  CAS  Google Scholar 

  • Goode BL, Feinstein SC (1994) Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau. J Cell Biol 124:769–782

    Article  PubMed  CAS  Google Scholar 

  • Graham JC, Oppenheimer DR (1969) Othostatic hypotension and nicotine sensitivity in a case of multiple system atrophy. J Neurol Neurosurg Psychiat 32:28–34

    Article  PubMed  CAS  Google Scholar 

  • Greenberg SG, Davies P (1990) A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by Polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 87:5827–5831

    Article  PubMed  CAS  Google Scholar 

  • Grover A, Houlden H, Baker M, Adamson J, Lewis J, Prihar G, Pickering-Brown S, Duff K, Hutton M (1999) 5′ Splice site mutations in tau associated with the inherited dementia FTDP-17 affect a stem-loop structure that regulates alternative splicing of exon 10. J Biol Chem 274:15134–15143

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa M, Crowther RA, Jakes R, Goedert M (1997) Alzheimer-like changes in microtubule-associated protein tau induced by sulfated glycosaminoglycans. Inhibition of microtubule binding, stimulation of phosphorylation, and filament assembly depend on the degree of sulfation. J Biol Chem 272:33118–33124

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa M, Smith MJ, Goedert M (1998) Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS Lett 437:207–210

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa M, Smith M J, Iijima M, Tabira T, Goedert M (1999) FTDP-17 mutations N279K and S305N in tau produce increased splicing of exon 10. FEBS Lett 443:93–96

    Article  PubMed  CAS  Google Scholar 

  • Hong M, Chen DCR, Klein PS, Lee VM-Y (1997) Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem 272:25326–25332

    Article  PubMed  CAS  Google Scholar 

  • Hong M, Zhukareva V, Vogelsberg-Ragaglia V, Wszolek Z, Reed L, Miller BI, Geschwind DH, Bird TD, McKeel D, Goate A, Morris JC, Wilhelmsen KC, Schellenberg GD, Trojanowski JQ, Lee VM-Y (1998) Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 282:1914–1917

    Article  PubMed  CAS  Google Scholar 

  • Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, Hillebrand M, Joosse M, Kwon JM, Nowotny P, Che LK, Norton J, Morris JC, Reed LA, Trojanowski J, Basun H, Lannfelt L, Neystat M, Fahn S, Dark F, Tannenberg T, Dodd PR, Hayward N, Kwok JBJ, Schofield PR, Andreadis A, Snowden J, Craufurd D, Neary D, Owen F, Oostra BA, Hardy J, Goate A, Van Swieten J, Mann D, Lynch T, Heutink P (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705

    Article  PubMed  CAS  Google Scholar 

  • Iijima M, Tabira T, Poorkaj P, Schellenberg GD, Trojanowski JQ, Lee VM-Y, Schmidt ML, Takahashi K, Nabika T, Matsumoto T, Yamashita Y, Yoshioka S, Ishino H (1999) A distinct familial presenile dementia with a novel missense mutation in the tau gene. Neuro Report 10:497–501

    CAS  Google Scholar 

  • Ince PG, Perry EWK, Morris CM (1998) Dementia with Lewy bodies: A distinct non-Alzheimer dementia syndrome? Brain Pathol 8:299–324

    Article  PubMed  CAS  Google Scholar 

  • Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345:27–32

    Article  PubMed  CAS  Google Scholar 

  • Jensen PH, Nielsen MH, Jakes R, Dotti CG, Goedert M (1998) Binding of a-synuclein to rat brain vesicles is abolished by familial Parkinson’s disease mutation. J Biol Chem 273:26292–26294

    Article  PubMed  CAS  Google Scholar 

  • Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G, Joseph BK, Rosen C, Shi YE (1998) Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing. Cancer Res 57:759–764

    Google Scholar 

  • Kampers T, Friedhoff P, Biernat J, Mandelkow EM, Mandelkow E (1996) RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments. FEBS Lett 399:344–349

    Article  PubMed  CAS  Google Scholar 

  • Kato S, Nakamura H (1990) Cytoplasmic argyrophilic inclusions in neurons of pontine nuclei in patients with olivopontocerebellar atrophy: Immunohistochemical and ultrastructural studies. Acta Neuropathol 79:584–594

    Article  PubMed  CAS  Google Scholar 

  • Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, Przuntek H, Epplen JT, Schös L, Riess O (1998) Alabo Pro mutation in the gene encoding a-synuclein in Parkinson’s disease. Nature Genet 18:106–108

    Article  PubMed  Google Scholar 

  • Lee VM-Y, Balin BJ, Otvos L, Trojanowski JQ (1991) A68 — a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251:675–678

    Article  PubMed  CAS  Google Scholar 

  • Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998) Alpha synuclein in neurodegenerative disorders: murderer or accomplice? Nature Med 4:755–757

    Article  PubMed  CAS  Google Scholar 

  • Mirra SS, Murrell JR, Gearing M, Spillantini MG, Goedert M, Crowther RA, Levey AI, Jones R, Green J, Shoffner JM, Wainer BH, Schmidt ML, Trojanowski JQ, Ghetti B (1999) Tau pathology in a family with dementia and a P301L mutation in tau. J Neuropathol Exp Neurol 58:335–345

    Article  PubMed  CAS  Google Scholar 

  • Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Titan K, Ihara Y (1995) Proline-directed and non-proline-directed phosphorylation of PHF-tau. J Biol Chem 270:823–829

    Article  PubMed  CAS  Google Scholar 

  • Morris HR, Perez-Tur J, Janssen JC, Brown J, Lees AJ, Wood NW, Hardy J, Hutton M, Rossor MN (1999) Mutation in the tau exon 10 splice site region in familial frontotemporal dementia. Ann Neurol 45:270–271

    Article  PubMed  CAS  Google Scholar 

  • Munoz-Montano JR, Moreno FJ, Avila J, Diaz-Nido J (1997) Lithium inhibits Alzheimer’s disease-like tau phosphorylation in neurons. FEBS Lett 411:183–188

    Article  PubMed  CAS  Google Scholar 

  • Nacharaju P, Lewis J, Easson C, Yen S, Hackett J, Hutton M, Yen S-H (1999) Accelerated filament formation from tau protein with specific FTDP-17 missense mutations. FEBS Lett 447:195–199

    Article  PubMed  CAS  Google Scholar 

  • Nakajo S, Tsukada K, Omata K, Nakamura Y, Nakaya K (1993) A new brain-specific 14-kDa protein is a phosphoprotein. Its complete amino acid sequence and evidence for phosphorylation. Eur J Bio-chem 217:1057–1063

    Article  CAS  Google Scholar 

  • Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy. J Neurol Sci 94:79–100

    Article  PubMed  CAS  Google Scholar 

  • Pérez M, Valpuesta JM, Medina M, Montejo de Garcini E, Avila J (1996) Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau interactions. J Neuro-chem 67:1183–1190

    Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WO, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the a-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

    Article  PubMed  CAS  Google Scholar 

  • Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WO, Raskind M, Schellenberg OD (1998) Tau is a candidate gene for chromosome 17 rontotemporal dementia. Ann Neurol 43:815–825

    Article  PubMed  CAS  Google Scholar 

  • Probst A, Tolnay M, Langui D, Goedert M, Spillantini MG (1996) Pick’s disease: hyperphosphorylated tau protein segregates to the somatoaxonal compartment. Acta Neuropathol 92:588–596

    Article  PubMed  CAS  Google Scholar 

  • Qi Z, Zhu X, Goedert M, Fujita DJ, Wang JH (1998) Effect of heparin on phosphorylation site specificity of neuronal Cdc2-like kinase. FEBS Lett 423:227–230

    Article  PubMed  CAS  Google Scholar 

  • Reed LA, Schmidt ML, Wszolek ZK, Balin BJ, Soontornniyomkij V, Lee VM-Y, Trojanowski JQ, Schelper RL (1998) The neuropathology of a chromosome 17-linked autosomal dominant Parkinsonism and dementia (pallido-ponto-nigral degeneration). J Neuropathol Exp Neurol 57:588–601

    Article  PubMed  CAS  Google Scholar 

  • Rizzu P, Van Swieten JC, Joosse M, Hasegawa M, Stevens M, Tibben A, Niermeijer MF, Hillebrand M, Ravid R, Oostra BA, Goedert M, Van Duijn CM, Heutink P (1999) High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Human Genet 64:414–421

    Article  CAS  Google Scholar 

  • Saudou F, Finkbeiner S, Devys D, Greenberg ME (1998) Huntingtin acts in the nucleus to induce apop-tosis but death does not correlate with the formation of intranuclear inclusions. Cell 95:55–66

    Article  PubMed  CAS  Google Scholar 

  • Schweers O, Schönbrunn-Hanebeck E, Marx A, Mandelkow E (1994) Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem 269:24290–24297

    PubMed  CAS  Google Scholar 

  • Sisodia SS (1998) Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial? Cell 95:1–4

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Crowther RA, Goedert M (1996) Comparison of the neurofibrillary pathology in Alzheimer’s disease and familial presenile dementia with tangles. Acta Neuropathol 92:42–48

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MJ, Ghetti B (1997a) Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci USA 94:4113–4118

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997b) α-Synuclein in Lewy bodies. Nature 388:839–840

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Bird TD, Ghetti B (1998a) Frontotemporal dementia and parkinsonism linked to chromosome 17: A new group of tauopathies. Brain Pathol 8:387–402

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998b) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 95:7737–7741

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Crowther RA, Kamphorst W, Heutink P, Van Swieten JC (1998c) Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am J Pathol 153:1359–1363

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998d) a-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95:6469–6473

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Crowther HA, Jakes R, Cairns NJ, Lantos PL, Goedert M (1998e) Filamentous a-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett 251:205–208

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Tolnay M, Love S, Goedert M (1999) Microtubule-associated protein tau, heparan sulphate and a-synuclein in several neurodegenerative diseases. Acta Neuropathol 97:585–594

    Article  PubMed  CAS  Google Scholar 

  • Takeda A, Mallory M, Sundsmo M, Honer W, Hansen L, Masliah E (1998) Abnormal accumulation of NACP/a-synuclein in neurodegenerative disorders. Am J Pathol 152:367–372

    PubMed  CAS  Google Scholar 

  • Tolnay M, Spillantini MG, Goedert M, Ulrich J, Langui D, Probst A (1997) Argyrophilic grain disease: widespread hyperphosphorylation of tau in limbic neurons. Acta Neuropathol 93:477–484

    Article  PubMed  CAS  Google Scholar 

  • Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM-Y (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble a-synuclein. Ann Neurol 44:415–422

    Article  PubMed  CAS  Google Scholar 

  • Uéda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DAC, Kondo J, Ihara Y, Saitoh T (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci USA 90:11282–11286

    Article  PubMed  Google Scholar 

  • Varani L, Hasegawa M, Spillantini MG, Smith MJ, Murrell JR, Ghetti B, Klug A, Goedert M, Varani G (1999) Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17. Proc Natl Acad Sci USA 96:8229–8234

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi K, Matsumoto K, Takayama K, Yoshimoto M, Takahashi H (1997) NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson’s disease. Neurosci Lett 239:45–48

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998a) α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi K, Hayashi S, Kakita A, Yamada M, Toyoshima Y, Yoshimoto M, Takahashi H (1998b) Accumulation of a-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy. Acta Neuropathol 96:445–452

    Article  PubMed  CAS  Google Scholar 

  • Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35:13710–13715

    Article  Google Scholar 

  • Wischik CM, Novak M, Thogersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci USA 85:4506–4510

    Article  PubMed  CAS  Google Scholar 

  • Yoshida H, Ihara Y (1993) Tau in paired helical filament is functionally distinct from fetal tau: assembly incompetence of paired helical filament tau. J Neurochem 61:1183–1186

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. M. Goedert
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  2. M. G. Spillantini
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Editors and Affiliations

  1. The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104-4283, USA

    V. M.-Y. Lee  & J. Q. Trojanowski  & 

  2. INSERM U422, Place der Verdun, 59045, Lille, France

    L. Buée

  3. Pour la Recherche Thérapeutique, Fondation IPSEN, 24, rue Erlanger, 75781, Paris Cedex 16, France

    Y. Christen Ph. D.

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Goedert, M., Spillantini, M.G. (2000). Tauopathies and α-Synucleinopathies. In: Lee, V.MY., Trojanowski, J.Q., Buée, L., Christen, Y. (eds) Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders. Research and Perspectives in Alzheimer’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04056-0_6

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  • DOI: https://doi.org/10.1007/978-3-662-04056-0_6

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