1932

Abstract

A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

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2017-07-25
2024-06-25
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Literature Cited

  1. Ahmed Z, Cooper J, Murray TK, Garn K, McNaughton E. et al. 2014. A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: The pattern of spread is determined by connectivity, not proximity. Acta Neuropathol 127:667–83 [Google Scholar]
  2. Aizawa H, Emori Y, Murofushi H, Kawasaki H, Sakai H, Suzuki K. 1990. Molecular cloning of a ubiquitously distributed microtubule-associated protein with Mr 190,000. J. Biol. Chem. 265:13849–55 [Google Scholar]
  3. Allen B, Ingram E, Takao M, Smith MJ, Jakes R. et al. 2002. Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22:9340–51 [Google Scholar]
  4. Alzheimer A. 1907. Über eine eigenartige Erkrankung der Hirnrinde. Allg. Z. Psychiatr. 22:146–48 [Google Scholar]
  5. Alzheimer A. 1911. Über eigenartige Krankheitsfälle des späteren Alters. Z. Gesamte Neurol. Psychiatr. 4:356–85 [Google Scholar]
  6. Andorfer C, Kress Y, Espinoza M, de Silva R, Tucker KL. et al. 2003. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J. Neurochem. 86:582–90 [Google Scholar]
  7. Andronesi OC, Von Bergen M, Biernat J, Seidel K, Griesinger C. et al. 2008. Characterization of Alzheimer's-like paired helical filaments from the core domain of tau protein using solid-state NMR spectroscopy. J. Am. Chem. Soc. 130:5922–28 [Google Scholar]
  8. Arendt T, Stieler J, Holzer M. 2016. Tau and tauopathies. Brain Res. Rev. 126:238–92 [Google Scholar]
  9. Arendt T, Stieler J, Strijkstra AM, Hut RA, Rüdiger J. et al. 2003. Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J. Neurosci. 23:6972–81 [Google Scholar]
  10. Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J. et al. 2015. Depletion of microglia and inhibition of exosome synthesis halt tau progression. Nat. Neurosci. 18:1584–93 [Google Scholar]
  11. Baker M, Litvan I, Houlden H, Adamson J, Dickson D. et al. 1999. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum. Mol. Genet. 8:711–15 [Google Scholar]
  12. Bellucci A, Westwood AJ, Ingram E, Casamenti F, Goedert M, Spillantini MG. 2004. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am. J. Pathol. 165:1643–52 [Google Scholar]
  13. Berger Z, Roder H, Hanna A, Carlson A, Rangachari V. et al. 2007. Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J. Neurosci. 27:3650–62 [Google Scholar]
  14. Berriman J, Serpell LC, Oberg KA, Fink AL, Goedert M, Crowther RA. 2003. Tau filaments from human brain and from in vitro assembly of recombinant protein show cross-β structure. PNAS 100:9034–38 [Google Scholar]
  15. Boluda S, Iba M, Zhang B, Raible KM, Lee VMY. et al. 2015. Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer's disease or corticobasal degeneration. Acta Neuropathol 129:221–37 [Google Scholar]
  16. Bondareff W, Harrington C, Wischik CM, Hauser DL, Roth M. 1994. Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 53:158–64 [Google Scholar]
  17. Braak H, Braak E. 1991. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–59 [Google Scholar]
  18. Braak H, Del Tredici K. 2011. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol 121:171–81 [Google Scholar]
  19. Buée-Scherrer V, Buée L, Leveugle B, Perl DP, Vermersch P. et al. 1997. Pathological tau protein in post-encephalitic parkinsonism: comparison with Alzheimer's disease and other neurodegenerative disorders. Ann. Neurol. 42:356–59 [Google Scholar]
  20. Caffrey TM, Joachim C, Wade-Martins R. 2008. Haplotype-specific expression of the N-terminal exon 2 and 3 at the human MAPT locus. Neurobiol. Aging 29:1923–29 [Google Scholar]
  21. Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G. et al. 2015. Synaptic contacts enhance cell-to-cell tau pathology propagation. Cell Rep 11:1176–83 [Google Scholar]
  22. Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S. et al. 2013a. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. PNAS 110:9535–40 [Google Scholar]
  23. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S. et al. 2009. Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 11:909–13 [Google Scholar]
  24. Clavaguera F, Hench J, Lavenir I, Schweighauser G, Frank S. et al. 2014. Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice. Acta Neuropathol 127:299–301 [Google Scholar]
  25. Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M. 2013b. “Prion-like” templated misfolding in tauopathies. Brain Pathol 23:342–49 [Google Scholar]
  26. Conrad C, Andreadis A, Trojanowski JQ, Dickson DW, Kang D. et al. 1997. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann. Neurol. 41:277–81 [Google Scholar]
  27. Coppola G, Chinnathambi S, Lee JJ, Dombroski BA, Baker MC. et al. 2012. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases. Hum. Mol. Genet. 21:3500–12 [Google Scholar]
  28. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC. et al. 1993. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261:921–23 [Google Scholar]
  29. Couchie D, Mavilia C, Georgieff IS, Liem RKH, Shelanski ML, Nunez J. 1992. Primary structure of high molecular weight tau present in the peripheral nervous system. PNAS 89:4378–81 [Google Scholar]
  30. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL. et al. 2014. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128:755–66 [Google Scholar]
  31. Crowther RA. 1991. Straight and paired helical filaments in Alzheimer disease have a common structural unit. PNAS 88:2288–92 [Google Scholar]
  32. Crowther RA, Goedert M. 2000. Abnormal tau-containing filaments in neurodegenerative diseases. J. Struct. Biol. 130:271–79 [Google Scholar]
  33. Daebel V, Chinnathambi S, Biernat J, Schwalbe M, Habenstein B. et al. 2012. β-Sheet core of tau paired helical filaments revealed by solid-state NMR. J. Am. Chem. Soc. 134:13982–89 [Google Scholar]
  34. de Calignon A, Polydoro N, Suárez-Calvet M, Williams C, Adamowicz DH. et al. 2012. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73:685–97 [Google Scholar]
  35. Delacourte A, Robitaille Y, Sergeant N, Buée L, Hof PR. et al. 1996. Specific pathological tau protein variants characterize Pick's disease. J. Neuropathol. Exp. Neurol. 55:159–68 [Google Scholar]
  36. Dujardin S, Lécolle K, Caillierez R, Bégard S, Zommer N. et al. 2014. Neuron-to-neuron wild-type tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. Acta Neuropathol. Commun. 2:14 [Google Scholar]
  37. Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K. et al. 2015. PART is part of Alzheimer disease. Acta Neuropathol 129:749–56 [Google Scholar]
  38. Duyckaerts C, Uchihara T, Seilhean D, He Y, Hauw JJ. 1997. Dissociation of Alzheimer type pathology in a disconnected piece of cortex. Acta Neuropathol 93:501–7 [Google Scholar]
  39. Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA. et al. 2010. Peripherally applied Aβ-containing inoculates induce cerebral β-amyloidosis. Science 330:980–82 [Google Scholar]
  40. Eisenberg D, Jucker M. 2012. The amyloid state of proteins in human diseases. Cell 148:1188–203 [Google Scholar]
  41. Elbaum-Garfinkle S, Rhoades E. 2012. Identification of an aggregation-prone structure of tau. J. Am. Chem. Soc. 134:16607–13 [Google Scholar]
  42. Falcon B, Cavallini A, Angers R, Glover S, Murray TK. et al. 2015. Conformation determines the seeding potencies of native and recombinant tau aggregates. J. Biol. Chem. 290:1049–65 [Google Scholar]
  43. Fischer O. 1907. Miliare Nekrose mit drusigen Wucherungen der Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei seniler Demenz. Monatsschrift Psychiatr. Neurol. 22:361–72 [Google Scholar]
  44. Flament S, Delacourte A, Verny M, Hauw JJ, Javoy-Agid F. 1991. Abnormal tau proteins in progressive supranuclear palsy. Acta Neuropathol 81:591–96 [Google Scholar]
  45. Fontaine SN, Zheng D, Sabbagh JJ, Martin MM, Chaput D. et al. 2016. DNAJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. EMBO J 35:1537–49 [Google Scholar]
  46. Frost B, Jacks RL, Diamond MI. 2009. Propagation of tau misfolding from the outside to the inside of a cell. J. Biol. Chem. 284:12845–52 [Google Scholar]
  47. Fu H, Hussaini SA, Wegmann S, Profaci C, Daniels JD. et al. 2016. 3D visualization of the temporal and spatial spread of tau pathology reveals extensive sites of tau accumulation associated with neuronal loss and recognition memory deficit in aged tau transgenic mice. PLOS ONE 11:e0159463 [Google Scholar]
  48. Gans A. 1922. Betrachtungen über Art und Ausbreitung des krankhaften Prozesses in einem Fall von Pickscher Atrophie des Stirnhirns. Z. Gesamte Neurol. Psychiatr. 170:311–30 [Google Scholar]
  49. Ghetti B, Oblak AL, Boeve BF, Johnson KA, Dickerson BC, Goedert M. 2015. Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol. Appl. Neurobiol. 41:24–46 [Google Scholar]
  50. Goedert M. 2015. Alzheimer's and Parkinson's diseases: the prion concept in relation to assembled Aβ, tau, and α-synuclein. Science 349:1255555 [Google Scholar]
  51. Goedert M, Baur CP, Ahringer J, Jakes R, Hasegawa M. et al. 1996a. PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J. Cell Sci. 109:2661–72 [Google Scholar]
  52. Goedert M, Falcon B, Clavaguera F, Tolnay M. 2014. Prion-like mechanisms in the pathogenesis of tauopathies and synucleinopathies. Curr. Neurol. Neurosci. Rep. 14:495 [Google Scholar]
  53. Goedert M, Jakes R. 1990. Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. EMBO J 9:4225–30 [Google Scholar]
  54. Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ. et al. 1996b. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 383:550–53 [Google Scholar]
  55. Goedert M, Spillantini MG, Cairns NJ, Crowther RA. 1992a. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8:159–68 [Google Scholar]
  56. Goedert M, Spillantini MG, Crowther RA. 1992b. Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system. PNAS 89:1983–87 [Google Scholar]
  57. 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 3:519–26 [Google Scholar]
  58. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. 1988. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. PNAS 85:4051–55 [Google Scholar]
  59. Götz J, Probst A, Spillantini MG, Schäfer T, Jakes R. et al. 1995. Somatodendritic localisation and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform. EMBO J 14:1304–13 [Google Scholar]
  60. Hardy J, Selkoe DJ. 2002. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353–56 [Google Scholar]
  61. Harris JA, Koyama A, Maeda S, Ho K, Devidze N. et al. 2012. Human P301L-mutant tau expression in mouse entorhinal-hippocampal network causes tau aggregation and presynaptic pathology but no cognitive deficits. PLOS ONE 7:e45881 [Google Scholar]
  62. Heidary G, Fortini ME. 2001. Identification and characterization of the Drosophila tau homolog. Mech. Dev. 108:171–78 [Google Scholar]
  63. Höglinger GU, Melhem NM, Dickson DW, Sleiman PM, Wang LS. et al. 2011. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43:699–705 [Google Scholar]
  64. Holmes BB, De Vos SL, Kfoury N, Li M, Jacks R. et al. 2013. Heparan sulphate proteoglycans mediate internalization and propagation of specific proteopathic seeds. PNAS 110:E3138–47 [Google Scholar]
  65. Houlden H, Baker M, Morris HR, MacDonald N, Pickering-Brown S. et al. 2001. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 56:1702–6 [Google Scholar]
  66. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S. et al. 1998. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–5 [Google Scholar]
  67. Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ. et al. 2013. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy. J. Neurosci. 33:1024–37 [Google Scholar]
  68. Iqbal K, Liu F, Gong CX. 2016. Tau and neurodegenerative disease: the story so far. Nat. Rev. Neurol. 12:15–27 [Google Scholar]
  69. Irwin DJ, Brettschneider J, McMillan CT, Cooper F, Olm C. et al. 2015. Deep clinical and neuropathological phenotyping of Pick disease. Ann. Neurol. 79:272–87 [Google Scholar]
  70. Jackson SJ, Kerridge C, Cooper J, Cavallini A, Falcon B. et al. 2016. Short fibrils constitute the major species of seed-competent tau in the brains of mice transgenic for human P301S tau. J. Neurosci. 36:762–72 [Google Scholar]
  71. Janning D, Igaev M, Sündermann F, Brühmann J, Beutel O. et al. 2014. Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons. Mol. Biol. Cell 25:3541–51 [Google Scholar]
  72. Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J. et al. 2016. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann. Neurol. 79:110–19 [Google Scholar]
  73. Kadavath H, Jaremko M, Jaremko L, Biernat J, Mandelkow E. et al. 2015. Folding of tau protein on microtubules. Angew. Chem. Int. Ed. 54:10347–51 [Google Scholar]
  74. Kara E, Ling H, Pittman AM, Shaw K, de Silva R. et al. 2012. The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features. Neurobiol. Aging 33:2231.e7–14 [Google Scholar]
  75. Kidd M. 1963. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197:192–94 [Google Scholar]
  76. Kouri N, Ross OA, Dombroski B, Younkin CS, Serrie DJ. et al. 2015. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nat. Commun. 6:7247 [Google Scholar]
  77. Kovacs GG, Ferrer I, Grinberg LT, Alazuloff I, Attems J. et al. 2016. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy. Acta Neuropathol 131:87–102 [Google Scholar]
  78. Kovacs GG, Majtenyi K, Spina S, Murrell JR, Gelpi E. et al. 2008. White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration. J. Neuropathol. Exp. Neurol. 67:963–75 [Google Scholar]
  79. Kovacs GG, Wöhrer A, Ströbel T, Botond G, Attems J. et al. 2011. Unclassifiable tauopathy associated with an A152T variation in MAPT exon 7. Clin. Neuropathol. 30:3–10 [Google Scholar]
  80. Ksiezak-Reding H, Morgan K, Mattiace LA, Davies P, Liu WK. et al. 1994. Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. Am. J. Pathol. 145:1496–508 [Google Scholar]
  81. Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Sarmiento J, Troncoso J. et al. 2012. Identification of oligomers at early stages of tau aggregation in Alzheimer's disease. FASEB J 26:1946–59 [Google Scholar]
  82. Lee VMY, Goedert M, Trojanowski JQ. 2001. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24:1121–59 [Google Scholar]
  83. Lewis SA, Wang D, Cowan NJ. 1988. Microtubule-associated protein MAP2 shares a microtubule binding motif with tau protein. Science 242:936–39 [Google Scholar]
  84. Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P. et al. 2000. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25:402–5 [Google Scholar]
  85. Liu L, Drouet V, Wu JW, Witter MP, Small SA. et al. 2012. Trans-synaptic spread of tau pathology in vivo. PLOS ONE 7:e31302 [Google Scholar]
  86. Luk KC, Kehm VM, Zhang B, O'Brien P, Trojanowski JQ. et al. 2012. Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice. J. Exp. Med. 209:975–86 [Google Scholar]
  87. Maeda S, Sahara N, Saito Y, Murayama S, Ikai A. et al. 2006. Increased levels of granular tau oligomers: an early sign of brain aging and Alzheimer's disease. Neurosci. Res. 54:197–201 [Google Scholar]
  88. McEwan WA, Falcon B, Vaysburd M, Clift D, Oblak AL. et al. 2017. Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation. PNAS 114:574–79 [Google Scholar]
  89. McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE. et al. 2013. The spectrum of disease in chronic traumatic encephalopathy. Brain 136:43–64 [Google Scholar]
  90. Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C. et al. 2006. Exogenous induction of cerebral β-amyloidogenesis is governed by agent and host. Science 313:1781–84 [Google Scholar]
  91. Morozova OA, March ZM, Robinson AS, Colby DW. 2013. Conformational features of tau fibrils from Alzheimer's disease brain are faithfully propagated by unmodified recombinant protein. Biochemistry 52:6960–67 [Google Scholar]
  92. Morris M, Knudsen GM, Maeda S, Trinidad JC, Ioanoviciu A. et al. 2015. Tau post-translational modifications in wild-type and human amyloid precursor protein transgenic mice. Nat. Neurosci. 18:1183–89 [Google Scholar]
  93. Morsch R, Simon W, Coleman PD. 1999. Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 58:188–97 [Google Scholar]
  94. Murrell JR, Spillantini MG, Zolo P, Guazzelli M, Smith MJ. et al. 1999. Tau gene mutation G389R causes a tauopathy with abundant Pick body-like inclusions and axonal deposits. J. Neuropathol. Exp. Neurol. 58:1207–26 [Google Scholar]
  95. Neumann M, Diekmann S, Bertsch U, Vanmassenhove B, Bogerts B. et al. 2005. Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia. Neurogenetics 6:91–95 [Google Scholar]
  96. Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA. 1986. Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res 387:271–80 [Google Scholar]
  97. Niewidok B, Igaev M, Sündermann F, Janning D, Bakota L, Brandt R. 2016. Presence of a carboxy-terminal pseudorepeat and disease-like pseudophosphorylation critically influence tau's interaction with microtubules in axon-like processes. Mol. Biol. Cell 27:3537–49 [Google Scholar]
  98. Onari K, Spatz H. 1926. Anatomische Beiträge zur Lehre von der Pickschen umschriebenen Grosshirnrinden-Atrophie (“Picksche Krankheit”). Z. Gesamte Neurol. Psychiatr. 101:470–511 [Google Scholar]
  99. Ozcelik S, Sprenger F, Skachokova Z, Fraser G, Abramowski D. et al. 2016. Co-expression of truncated and full-length tau induces severe neurotoxicity. Mol. Psychiatry 21:1790–98 [Google Scholar]
  100. Paloneva J, Kestilä M, Wu J, Salminen A, Böhling T. et al. 2000. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat. Genet 25:357–61 [Google Scholar]
  101. Pastor P, Ezquerra M, Munoz E, Marti MJ, Blesa R. et al. 2000. Significant association between the tau gene A0/A0 genotype and Parkinson's disease. Ann. Neurol. 47:242–45 [Google Scholar]
  102. Pastor P, Moreno F, Clarimón J, Ruiz A, Combarros O. et al. 2015. MAPT H1 haplotype is associated with late-onset Alzheimer's disease risk in APOEɛ4 noncarriers: results from the dementia genetics Spanish consortium. J. Alzheimer's Dis. 49:343–52 [Google Scholar]
  103. 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 interaction. J. Neurochem. 67:1183–90 [Google Scholar]
  104. Pickering-Brown SM, Baker M, Nonaka T, Ikeda K, Sharma S. et al. 2004. Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene. Brain 127:1415–26 [Google Scholar]
  105. Pieri L, Madiona K, Bousset L, Melki R. 2012. Fibrillar α-synuclein and huntingtin exon 1 assemblies are toxic to cells. Biophys. J. 102:2894–905 [Google Scholar]
  106. Pooler AM, Phillips EC, Lau DH, Noble W, Hanger DP. 2013. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14:389–94 [Google Scholar]
  107. Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM. et al. 1998. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43:815–25 [Google Scholar]
  108. Probst A, Götz J, Wiederhold KH, Tolnay M, Mistl C. et al. 2000. Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol 99:469–81 [Google Scholar]
  109. Prusiner SB. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216:136–44 [Google Scholar]
  110. Prusiner SB. 2013. Biology and genetics of prions causing neurodegeneration. Annu. Rev. Genet. 47:601–23 [Google Scholar]
  111. Rademakers R, Baker M, Nicholson AM, Rutherford NJ, Finch N. et al. 2012. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leucoencephalopathy with spheroids. Nat. Genet. 44:200–5 [Google Scholar]
  112. Ramachandran G, Udgaonkar JB. 2011. Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by tau protein. J. Biol. Chem. 286:38948–59 [Google Scholar]
  113. Rao MV, McBrayer MK, Campbell J, Kumar A, Hashim A. et al. 2014. Specific calpain inhibition by calpastatin prevents tauopathy and neurodegeneration and restores normal lifespan in tau P301L mice. J. Neurosci. 34:9222–34 [Google Scholar]
  114. Recasens A, Dehay B, Bové J, Carballo-Carbajal I, Dovero S. et al. 2014. Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann. Neurol. 75:351–62 [Google Scholar]
  115. Rewcastle NB, Ball MJ. 1968. Electron microscopic structure of the “inclusion bodies” in Pick's disease. Neurology 18:1205–13 [Google Scholar]
  116. Sacino AN, Brooks M, Thomas MA, McKinney AB, Lee S. et al. 2014. Intramuscular injection of α-synuclein induces CNS α-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. PNAS 111:10732–37 [Google Scholar]
  117. Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N. et al. 2004. Staging of argyrophilic grains: an age-associated tauopathy. J. Neuropathol. Exp. Neurol. 63:911–18 [Google Scholar]
  118. Sanders DW, Kaufman SK, De Vos SL, Sharma AM, Mirhaba H. et al. 2014. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:1271–88 [Google Scholar]
  119. Sankaranarayanan S, Barten DM, Vana L, Devidze N, Yang L. et al. 2015. Passive immunization with phospho-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models. PLOS ONE 10:e0125614 [Google Scholar]
  120. SantaCruz K, Lewis J, Spires T, Paulson J, Kotilinek L. et al. 2005. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476–81 [Google Scholar]
  121. Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C. et al. 2009. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet. 41:1303–7 [Google Scholar]
  122. Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA. et al. 2007. Atomic structures of amyloid cross-β spines reveal varied steric zippers. Nature 447:453–57 [Google Scholar]
  123. Schmidt ML, Zhukareva V, Newell KL, Lee VMY, Trojanowski JQ. 2001. Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease. Acta Neuropathol 101:518–24 [Google Scholar]
  124. Schöll M, Lockhart SN, Schonhaut DR, O'Neil JP, Janabi M. et al. 2016. PET imaging of tau deposition in the aging human brain. Neuron 89:971–82 [Google Scholar]
  125. Siman R, Lin YG, Malthankar-Phatak G, Dong Y. 2013. A rapid gene delivery–based mouse model for early-stage Alzheimer's disease–type tauopathy. J. Neuropathol. Exp. Neurol. 72:1062–71 [Google Scholar]
  126. Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR. et al. 2009. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 41:1308–12 [Google Scholar]
  127. 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 [Google Scholar]
  128. Spillantini MG, Crowther RA, Kamphorst W, Heutink P, van Swieten JC. 1998a. Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am. J. Pathol. 153:1359–63 [Google Scholar]
  129. Spillantini MG, Goedert M. 2013. Tau pathology and neurodegeneration. Lancet Neurol 12:609–22 [Google Scholar]
  130. Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B. 1997. Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments. PNAS 94:4113–18 [Google Scholar]
  131. Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A. et al. 1998b. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. PNAS 94:4113–18 [Google Scholar]
  132. Spina S, Murrell JR, Yoshida H, Ghetti B, Bermingham N. et al. 2007. The novel Tau mutation G335S: clinical, neuropathological and molecular characterization. Acta Neuropathol 113:461–70 [Google Scholar]
  133. Spires TL, Orne JD, SantaCruz K, Pitstick R, Carlson GA. et al. 2006. Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am. J. Pathol. 168:1598–607 [Google Scholar]
  134. Stefansson H, Helgason A, Thorleifsson G, Steinthorsdottir V, Masson G. et al. 2005. A common inversion under selection in Europeans. Nat. Genet. 37:129–37 [Google Scholar]
  135. Stertz G. 1926. Über die Picksche Atrophie. Z. Gesamte Neurol. Psychiatr. 101:729–49 [Google Scholar]
  136. Stöhr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK. et al. 2012. Purified and synthetic Alzheimer's amyloid-beta (Aβ) prions. PNAS 109:11025–30 [Google Scholar]
  137. Sündermann F, Fernandez MP, Morgan RO. 2016. An evolutionary roadmap to the microtubule-associated protein MAP Tau. BMC Genom. 17:264 [Google Scholar]
  138. Tacik P, DeTure M, Hinkle KM, Lin WL, Sanchez-Contreras M. et al. 2015. A novel tau mutation in exon 12, p.Q336H, causes hereditary Pick disease. J. Neuropathol. Exp. Neurol. 74:1042–52 [Google Scholar]
  139. Togo T, Sahara N, Yen SH, Cookson N, Ishizawa T. et al. 2002. Argyrophilic grain disease is a sporadic 4-repeat tauopathy. J. Neuropathol. Exp. Neurol. 61:547–66 [Google Scholar]
  140. Uchihara T, Tsuchiya K, Nakamura A, Akiyama H. 2005. Argyrophilic grains are not always argyrophilic—distinction from neurofibrillary tangles of diffuse neurofibrillary tangles with calcification revealed by comparison between Gallyas and Campbell-Switzer methods. Acta Neuropathol 110:158–64 [Google Scholar]
  141. Ulrich J. 1985. Alzheimer changes in nondemented patients younger than sixty-five: possible early stages of Alzheimer's disease and senile dementia of Alzheimer type. Ann. Neurol. 17:273–77 [Google Scholar]
  142. Ulrich J, Spillantini MG, Goedert M, Dukas L, Stähelin HB. 1992. Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegeneration 1:257–64 [Google Scholar]
  143. Usenovic M, Niroomand S, Drolet SE, Yao L, Gaspar RC. et al. 2015. Internalized tau oligomers cause neurodegeneration by inducing accumulation of pathogenic tau in human neurons derived from induced pluripotent stem cells. J. Neurosci. 35:14234–50 [Google Scholar]
  144. Valenca GT, Srivastava GP, Oliveiro-Filho J, White CC, Yu L. et al. 2016. The role of MAPT haplotype H2 and isoform 1N/4R in parkinsonism of older adults. PLOS ONE 11:e0157452 [Google Scholar]
  145. Verheyen A, Diels A, Dijkmans J, Oyelami T, Meneghelio G. et al. 2015. Using human iPSC-derived neurons to model TAU aggregation. PLOS ONE 10:e0146127 [Google Scholar]
  146. Von Bergen M, Barghorn S, Li L, Marx A, Biernat J. et al. 2001. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local β-structure. J. Biol. Chem. 276:48165–74 [Google Scholar]
  147. Von Bergen M, Friedhoff P, Biernat J, Heberle J, Mandelkow EM, Mandelkow E. 2000. Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure. PNAS 97:5129–34 [Google Scholar]
  148. Walsh DM, Selkoe DJ. 2016. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat. Rev. Neurosci. 17:251–60 [Google Scholar]
  149. Wegmann S, Maury EA, Kirk MJ, Saqran L, Roe A. et al. 2015. Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J 34:3028–41 [Google Scholar]
  150. Wilhelmsen KC, Lynch T, Pavlou E, Higgins M, Nygaard TG. 1994. Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21–22. Am. J. Hum. Genet. 55:1159–65 [Google Scholar]
  151. Wiltzius JJW, Landau M, Nelson R, Sawaya MR, Apostol MI. et al. 2009. Molecular mechanisms for protein-encoded inheritance. Nat. Struct. Mol. Biol. 16:973–78 [Google Scholar]
  152. Wischik CM, Novak M, Edwards PC, Klug A, Tichelaar W, Crowther RA. 1988a. Structural characterization of the core of the paired helical filament of Alzheimer disease. PNAS 85:4884–88 [Google Scholar]
  153. Wischik CM, Novak M, Thogersen HC, Edwards PC, Runswick MJ, Jakes R. et al. 1988b. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. PNAS 85:4506–10 [Google Scholar]
  154. Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J. et al. 2001. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711–14 [Google Scholar]
  155. Wu JW, Hussaini SA, Bastille IM, Rodriguez GA, Mrejeru A. et al. 2016. Neuronal activity enhances tau propagation and tau pathology in vivo. Nat. Neurosci. 19:1085–92 [Google Scholar]
  156. Xie C, Soeda Y, Shinzaki Y, In Y, Tomoo K. et al. 2015. Identification of key amino acids responsible for the distinct aggregation properties of microtubule-associated protein 2 and tau. J. Neurochem. 135:19–26 [Google Scholar]
  157. Yamada K, Cirrito JR, Stewart FR, Jian H, Finn MB. et al. 2011. In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice. J. Neurosci. 31:13110–17 [Google Scholar]
  158. Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE. et al. 2014. Neuronal activity regulates extracellular tau in vivo. J. Exp. Med. 211:387–93 [Google Scholar]
  159. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S. et al. 2014. Anti-tau antibodies that block aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80:402–14 [Google Scholar]
  160. Yetman MJ, Lillehaug S, Bjaalie JG, Leergaard TB, Jankowsky JL. 2016. Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex. Brain Struct. Funct. 221:2231–49 [Google Scholar]
  161. Yoshida H, Goedert M. 2002. Molecular cloning and functional characterization of chicken brain tau: isoforms with up to five tandem repeats. Biochemistry 41:15203–11 [Google Scholar]
  162. Zhang B, Une Y, Fu X, Yan J, Ge FX. et al. 2008. Fecal transmission of AA amyloidosis in the cheetah contributes to high incidence of disease. PNAS 105:7263–68 [Google Scholar]
  163. Zhao Y, Tseng IC, Heyser CJ, Rockenstein E, Mante M. et al. 2015. Appoptosin-mediated caspase cleavage of tau contributes to progressive supranuclear palsy pathogenesis. Neuron 87:963–75 [Google Scholar]
  164. Zhong Q, Condon EE, Nagaraja HN, Kuret J. 2012. Tau isoform composition influences rate and extent of filament formation. J. Biol. Chem. 287:20711–19 [Google Scholar]
  165. Zhou J, Gennatas ED, Kramer JH, Miller BL, Seeley WW. 2012. Predicting regional neurodegeneration from the healthy brain functional connectome. Neuron 73:1216–27 [Google Scholar]
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