Skip to main content
SpringerLink
Log in

Tau Prion-Like Propagation: State of the Art and Current Challenges

  • Chapter
  • First Online:
Book cover Tau Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1184))

Abstract

It has been almost a decade since the hypothesis of active tau protein propagation in Alzheimer’s disease and associated tauopathies was formally raised. We view tau propagation as a cascade of events, starting with early tau misfolding, followed by transfer to another, anatomically connected, cell, contaminating in corruption of endogenous tau in the recipient cell through a seeding mechanism of templated misfolding. These mechanisms are very similar to those of other proteinopathies and to ideas about how prion pathologies spread through the brain. Nonetheless, the specific mechanisms underlying each of these steps remains uncertain and is a fertile ground for new experimental approaches potentially requiring new experimental models. We review, here, the state of the art of the research on tau prion-like propagation and we highlight some key challenges to understanding the detailed mechanisms of cell to cell propagation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abounit S, Wu JW, Duff K, Victoria GS, Zurzolo C. Tunneling nanotubes: a possible highway in the spreading of tau and other prion-like proteins in neurodegenerative diseases. Prion. 2016;10(5):344–51. https://doi.org/10.1080/19336896.2016.1223003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Adams SJ, DeTure MA, McBride M, Dickson DW, Petrucelli L. Three repeat isoforms of tau inhibit assembly of four repeat tau filaments. PLoS One. 2010;5(5):e10810. https://doi.org/10.1371/journal.pone.0010810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aguzzi A, Rajendran L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron. 2009;64(6):783–90. https://doi.org/10.1016/j.neuron.2009.12.016.

    Article  CAS  PubMed  Google Scholar 

  4. Ahmed Z, Cooper J, Murray TK, Garn K, McNaughton E, Clarke H, Parhizkar S, Ward MA, Cavallini A, Jackson S, Bose S, Clavaguera F, Tolnay M, Lavenir I, Goedert M, Hutton ML, O’Neill MJ. 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. 2014;127(5):667–83. https://doi.org/10.1007/s00401-014-1254-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341–5. https://doi.org/10.1038/nbt.1807.

    Article  CAS  PubMed  Google Scholar 

  6. Aoyagi H, Hasegawa M, Tamaoka A. Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau but not wild-type tau. J Biol Chem. 2007;282(28):20309–18. https://doi.org/10.1074/jbc.M611876200.

    Article  CAS  PubMed  Google Scholar 

  7. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW. The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer’s disease. Cereb Cortex. 1991;1(1):103–16.

    Article  CAS  PubMed  Google Scholar 

  8. Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, Wolozin B, Butovsky O, Kugler S, Ikezu T. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18(11):1584–93. https://doi.org/10.1038/nn.4132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bennett RE, DeVos SL, Dujardin S, Corjuc B, Gor R, Gonzalez J, Roe AD, Frosch MP, Pitstick R, Carlson GA, Hyman BT. Enhanced Tau aggregation in the presence of amyloid beta. Am J Pathol. 2017;187(7):1601–12. https://doi.org/10.1016/j.ajpath.2017.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Blennow K. A review of fluid biomarkers for Alzheimer’s disease: moving from CSF to blood. Neurol Ther. 2017;6(Suppl 1):15–24. https://doi.org/10.1007/s40120-017-0073-9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bousset L, Pieri L, Ruiz-Arlandis G, Gath J, Jensen PH, Habenstein B, Madiona K, Olieric V, Bockmann A, Meier BH, Melki R. Structural and functional characterization of two alpha-synuclein strains. Nat Commun. 2013;4:2575. https://doi.org/10.1038/ncomms3575.

    Article  CAS  PubMed  Google Scholar 

  12. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.

    Article  CAS  PubMed  Google Scholar 

  13. Braak H, Del Tredici K. The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol. 2011;121(2):171–81. https://doi.org/10.1007/s00401-010-0789-4.

    Article  PubMed  Google Scholar 

  14. Caillierez R, Begard S, Lecolle K, Deramecourt V, Zommer N, Dujardin S, Loyens A, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Buee L, Colin M. Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain. Mol Ther. 2013;21(7):1358–68. https://doi.org/10.1038/mt.2013.66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G, de Strooper B, de Wit J, Verstreken P, Moechars D. Synaptic contacts enhance cell-to-cell Tau pathology propagation. Cell Rep. 2015;11(8):1176–83. https://doi.org/10.1016/j.celrep.2015.04.043.

    Article  CAS  PubMed  Google Scholar 

  16. Calafate S, Flavin W, Verstreken P, Moechars D. Loss of Bin1 promotes the propagation of Tau pathology. Cell Rep. 2016;17(4):931–40. https://doi.org/10.1016/j.celrep.2016.09.063.

    Article  CAS  PubMed  Google Scholar 

  17. Castillo-Carranza DL, Gerson JE, Sengupta U, Guerrero-Munoz MJ, Lasagna-Reeves CA, Kayed R. Specific targeting of tau oligomers in Htau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. J Alzheimers Dis. 2014;40(Suppl 1):S97–S111. https://doi.org/10.3233/JAD-132477.

    Article  CAS  PubMed  Google Scholar 

  18. Chai X, Dage JL, Citron M. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol Dis. 2012;48(3):356–66. https://doi.org/10.1016/j.nbd.2012.05.021.

    Article  CAS  PubMed  Google Scholar 

  19. Clavaguera F, Akatsu H, Fraser G, Crowther RA, Frank S, Hench J, Probst A, Winkler DT, Reichwald J, Staufenbiel M, Ghetti B, Goedert M, Tolnay M. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci U S A. 2013;110(23):9535–40. https://doi.org/10.1073/pnas.1301175110.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol. 2009;11(7):909–13. https://doi.org/10.1038/ncb1901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Clavaguera F, Hench J, Lavenir I, Schweighauser G, Frank S, Goedert M, Tolnay M. Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice. Acta Neuropathol. 2014;127(2):299–301. https://doi.org/10.1007/s00401-013-1231-5.

    Article  PubMed  Google Scholar 

  22. Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M. “Prion-like” templated misfolding in tauopathies. Brain Pathol. 2013;23(3):342–9. https://doi.org/10.1111/bpa.12044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Courade JP, Angers R, Mairet-Coello G, Pacico N, Tyson K, Lightwood D, Munro R, McMillan D, Griffin R, Baker T, Starkie D, Nan R, Westwood M, Mushikiwabo ML, Jung S, Odede G, Sweeney B, Popplewell A, Burgess G, Downey P, Citron M. Epitope determines efficacy of therapeutic anti-Tau antibodies in a functional assay with human Alzheimer Tau. Acta Neuropathol. 2018;136(5):729–45. https://doi.org/10.1007/s00401-018-1911-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dai CL, Hu W, Tung YC, Liu F, Gong CX, Iqbal K. Tau passive immunization blocks seeding and spread of Alzheimer hyperphosphorylated Tau-induced pathology in 3 x Tg-AD mice. Alzheimers Res Ther. 2018;10(1):13. https://doi.org/10.1186/s13195-018-0341-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. de Calignon A, Polydoro M, Suarez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron. 2012;73(4):685–97. https://doi.org/10.1016/j.neuron.2011.11.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Delacourte A, David JP, Sergeant N, Buee L, Wattez A, Vermersch P, Ghozali F, Fallet-Bianco C, Pasquier F, Lebert F, Petit H, Di Menza C. The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology. 1999;52(6):1158–65.

    Article  CAS  PubMed  Google Scholar 

  27. Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci U S A. 2009;106(31):13010–5. https://doi.org/10.1073/pnas.0903691106.

    Article  PubMed  PubMed Central  Google Scholar 

  28. DeVos SL, Corjuc BT, Commins C, Dujardin S, Bannon RN, Corjuc D, Moore BD, Bennett RE, Jorfi M, Gonzales JA, Dooley PM, Roe AD, Pitstick R, Irimia D, Frosch MP, Carlson GA, Hyman BT. Tau reduction in the presence of amyloid-beta prevents tau pathology and neuronal death in vivo. Brain. 2018;141(7):2194–212. https://doi.org/10.1093/brain/awy117.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Dujardin S. De la cellule au primate, propagation physiopathologique de la protéine Tau (From cells to primates, pathophysiological propagation of tau protein). Catalogue SCD Lille. 2015;2:1–334.

    Google Scholar 

  30. Dujardin S, Begard S, Caillierez R, Lachaud C, Carrier S, Lieger S, Gonzalez JA, Deramecourt V, Deglon N, Maurage CA, Frosch MP, Hyman BT, Colin M, Buee L. Different tau species lead to heterogeneous tau pathology propagation and misfolding. Acta Neuropathol Commun. 2018;6(1):132. https://doi.org/10.1186/s40478-018-0637-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Dujardin S, Begard S, Caillierez R, Lachaud C, Delattre L, Carrier S, Loyens A, Galas MC, Bousset L, Melki R, Auregan G, Hantraye P, Brouillet E, Buee L, Colin M. Ectosomes: a new mechanism for non-exosomal secretion of tau protein. PLoS One. 2014;9(6):e100760. https://doi.org/10.1371/journal.pone.0100760.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Dujardin S, Lecolle K, Caillierez R, Begard S, Zommer N, Lachaud C, Carrier S, Dufour N, Auregan G, Winderickx J, Hantraye P, Deglon N, Colin M, Buee L. Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies. Acta Neuropathol Commun. 2014;2:14. https://doi.org/10.1186/2051-5960-2-14.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Duyckaerts C, Hauw JJ. Diagnosis and staging of Alzheimer disease. Neurobiol Aging. 1997;18(4 Suppl):S33–42.

    Article  CAS  PubMed  Google Scholar 

  34. Falcon B, Cavallini A, Angers R, Glover S, Murray TK, Barnham L, Jackson S, O’Neill MJ, Isaacs AM, Hutton ML, Szekeres PG, Goedert M, Bose S. Conformation determines the seeding potencies of native and recombinant Tau aggregates. J Biol Chem. 2015;290(2):1049–65. https://doi.org/10.1074/jbc.M114.589309.

    Article  CAS  PubMed  Google Scholar 

  35. Falcon B, Noad J, McMahon H, Randow F, Goedert M. Galectin-8-mediated selective autophagy protects against seeded tau aggregation. J Biol Chem. 2018;293(7):2438–51. https://doi.org/10.1074/jbc.M117.809293.

    Article  CAS  PubMed  Google Scholar 

  36. Falcon B, Zhang W, Murzin AG, Murshudov G, Garringer HJ, Vidal R, Crowther RA, Ghetti B, Scheres SHW, Goedert M. Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature. 2018;561(7721):137–40. https://doi.org/10.1038/s41586-018-0454-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Faure J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B, Grange J, Schoehn G, Goldberg Y, Boyer V, Kirchhoff F, Raposo G, Garin J, Sadoul R. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006;31(4):642–8. https://doi.org/10.1016/j.mcn.2005.12.003.

    Article  CAS  PubMed  Google Scholar 

  38. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G. Cells release prions in association with exosomes. Proc Natl Acad Sci U S A. 2004;101(26):9683–8. https://doi.org/10.1073/pnas.0308413101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fitzpatrick AWP, Falcon B, He S, Murzin AG, Murshudov G, Garringer HJ, Crowther RA, Ghetti B, Goedert M, Scheres SHW. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature. 2017;547(7662):185–90. https://doi.org/10.1038/nature23002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Flavin WP, Bousset L, Green ZC, Chu Y, Skarpathiotis S, Chaney MJ, Kordower JH, Melki R, Campbell EM. Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins. Acta Neuropathol. 2017;134(4):629–53. https://doi.org/10.1007/s00401-017-1722-x.

    Article  CAS  PubMed  Google Scholar 

  41. Fontaine SN, Zheng D, Sabbagh JJ, Martin MD, Chaput D, Darling A, Trotter JH, Stothert AR, Nordhues BA, Lussier A, Baker J, Shelton L, Kahn M, Blair LJ, Stevens SM Jr, Dickey CA. DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. EMBO J. 2016;35(14):1537–49. https://doi.org/10.15252/embj.201593489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Forrest SL, Kril JJ, Halliday GM. Reply: will FTLD-tau work for all when FTDP-17 retires? Brain. 2018; https://doi.org/10.1093/brain/awy179.

    Article  PubMed  Google Scholar 

  43. Freundt EC, Maynard N, Clancy EK, Roy S, Bousset L, Sourigues Y, Covert M, Melki R, Kirkegaard K, Brahic M. Neuron-to-neuron transmission of alpha-synuclein fibrils through axonal transport. Ann Neurol. 2012;72(4):517–24. https://doi.org/10.1002/ana.23747.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Friedhoff P, von Bergen M, Mandelkow EM, Davies P, Mandelkow E. A nucleated assembly mechanism of Alzheimer paired helical filaments. Proc Natl Acad Sci U S A. 1998;95(26):15712–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Frost B, Diamond MI. Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci. 2010;11(3):155–9. https://doi.org/10.1038/nrn2786.

    Article  CAS  PubMed  Google Scholar 

  46. Frost B, Jacks RL, Diamond MI. Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem. 2009;284(19):12845–52. https://doi.org/10.1074/jbc.M808759200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Frost B, Ollesch J, Wille H, Diamond MI. Conformational diversity of wild-type Tau fibrils specified by templated conformation change. J Biol Chem. 2009;284(6):3546–51. https://doi.org/10.1074/jbc.M805627200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Furman JL, Holmes BB, Diamond MI. Sensitive detection of proteopathic seeding activity with FRET flow cytometry. J Vis Exp. 2015;106:e53205. https://doi.org/10.3791/53205.

    Article  Google Scholar 

  49. Furukawa Y, Kaneko K, Nukina N. Tau protein assembles into isoform- and disulfide-dependent polymorphic fibrils with distinct structural properties. J Biol Chem. 2011;286(31):27236–46. https://doi.org/10.1074/jbc.M111.248963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ghetti B, Oblak AL, Boeve BF, Johnson KA, Dickerson BC, Goedert M. Invited review: frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations: a chameleon for neuropathology and neuroimaging. Neuropathol Appl Neurobiol. 2015;41(1):24–46. https://doi.org/10.1111/nan.12213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology. 2003;60(9):1495–500.

    Article  CAS  PubMed  Google Scholar 

  52. Gibbons GS, Banks RA, Kim B, Xu H, Changolkar L, Leight SN, Riddle DM, Li C, Gathagan RJ, Brown HJ, Zhang B, Trojanowski JQ, Lee VM. GFP-mutant human Tau transgenic mice develop tauopathy following CNS injections of Alzheimer’s brain-derived pathological Tau or synthetic mutant human Tau fibrils. J Neurosci. 2017;37(47):11485–94. https://doi.org/10.1523/JNEUROSCI.2393-17.2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Goedert M, Clavaguera F, Tolnay M. The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci. 2010;33(7):317–25. https://doi.org/10.1016/j.tins.2010.04.003.

    Article  CAS  PubMed  Google Scholar 

  54. Gousset K, Schiff E, Langevin C, Marijanovic Z, Caputo A, Browman DT, Chenouard N, de Chaumont F, Martino A, Enninga J, Olivo-Marin JC, Mannel D, Zurzolo C. Prions hijack tunnelling nanotubes for intercellular spread. Nat Cell Biol. 2009;11(3):328–36. https://doi.org/10.1038/ncb1841.

    Article  CAS  PubMed  Google Scholar 

  55. Guo JL, Lee VM. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem. 2011;286(17):15317–31. https://doi.org/10.1074/jbc.M110.209296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hall GF, Patuto BA. Is tau ready for admission to the prion club? Prion. 2012;6(3):223–33. https://doi.org/10.4161/pri.19912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hall GF, Saman S. Death or secretion? The demise of a plausible assumption about CSF-tau in Alzheimer disease? Commun Integr Biol. 2012;5(6):623–6. https://doi.org/10.4161/cib.21437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hamaguchi T, Eisele YS, Varvel NH, Lamb BT, Walker LC, Jucker M. The presence of Abeta seeds, and not age per se, is critical to the initiation of Abeta deposition in the brain. Acta Neuropathol. 2012;123(1):31–7. https://doi.org/10.1007/s00401-011-0912-1.

    Article  CAS  PubMed  Google Scholar 

  59. He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L, Zhang B, Gathagan RJ, Yue C, Dengler C, Stieber A, Nitla M, Coulter DA, Abel T, Brunden KR, Trojanowski JQ, Lee VM. Amyloid-beta plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med. 2018;24(1):29–38. https://doi.org/10.1038/nm.4443.

    Article  CAS  PubMed  Google Scholar 

  60. Hoenig MC, Bischof GN, Seemiller J, Hammes J, Kukolja J, Onur OA, Jessen F, Fliessbach K, Neumaier B, Fink GR, van Eimeren T, Drzezga A. Networks of tau distribution in Alzheimer’s disease. Brain. 2018;141(2):568–81. https://doi.org/10.1093/brain/awx353.

    Article  PubMed  Google Scholar 

  61. Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, Ouidja MO, Brodsky FM, Marasa J, Bagchi DP, Kotzbauer PT, Miller TM, Papy-Garcia D, Diamond MI. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci U S A. 2013;110(33):E3138–47. https://doi.org/10.1073/pnas.1301440110.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Holmes BB, Furman JL, Mahan TE, Yamasaki TR, Mirbaha H, Eades WC, Belaygorod L, Cairns NJ, Holtzman DM, Diamond MI. Proteopathic tau seeding predicts tauopathy in vivo. Proc Natl Acad Sci U S A. 2014;111(41):E4376–85. https://doi.org/10.1073/pnas.1411649111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci U S A. 2009;106(48):20324–9. https://doi.org/10.1073/pnas.0911281106.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL. Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science. 1984;225(4667):1168–70.

    Article  CAS  PubMed  Google Scholar 

  65. Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ, Lee VM. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer’s-like tauopathy. J Neurosci. 2013;33(3):1024–37. https://doi.org/10.1523/JNEUROSCI.2642-12.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Iba M, McBride JD, Guo JL, Zhang B, Trojanowski JQ, Lee VM. Tau pathology spread in PS19 tau transgenic mice following locus coeruleus (LC) injections of synthetic tau fibrils is determined by the LC’s afferent and efferent connections. Acta Neuropathol. 2015;130(3):349–62. https://doi.org/10.1007/s00401-015-1458-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Irwin DJ, Brettschneider J, McMillan CT, Cooper F, Olm C, Arnold SE, Van Deerlin VM, Seeley WW, Miller BL, Lee EB, Lee VM, Grossman M, Trojanowski JQ. Deep clinical and neuropathological phenotyping of Pick disease. Ann Neurol. 2016;79(2):272–87. https://doi.org/10.1002/ana.24559.

    Article  CAS  PubMed  Google Scholar 

  68. Jackson SJ, Kerridge C, Cooper J, Cavallini A, Falcon B, Cella CV, Landi A, Szekeres PG, Murray TK, Ahmed Z, Goedert M, Hutton M, O’Neill MJ, Bose S. Short fibrils constitute the major species of seed-competent Tau in the brains of mice transgenic for human P301S Tau. J Neurosci. 2016;36(3):762–72. https://doi.org/10.1523/JNEUROSCI.3542-15.2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jacobs HIL, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals. Nat Neurosci. 2018;21(3):424–31. https://doi.org/10.1038/s41593-018-0070-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jarrett JT, Lansbury PT Jr. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie? Cell. 1993;73(6):1055–8.

    Article  CAS  PubMed  Google Scholar 

  71. Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J, Rentz D, Mormino E, Chhatwal J, Amariglio R, Papp K, Marshall G, Albers M, Mauro S, Pepin L, Alverio J, Judge K, Philiossaint M, Shoup T, Yokell D, Dickerson B, Gomez-Isla T, Hyman B, Vasdev N, Sperling R. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016;79(1):110–9. https://doi.org/10.1002/ana.24546.

    Article  PubMed  Google Scholar 

  72. Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 2013;501(7465):45–51. https://doi.org/10.1038/nature12481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kane MD, Lipinski WJ, Callahan MJ, Bian F, Durham RA, Schwarz RD, Roher AE, Walker LC. Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice. J Neurosci. 2000;20(10):3606–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kanmert D, Cantlon A, Muratore CR, Jin M, O’Malley TT, Lee G, Young-Pearse TL, Selkoe DJ, Walsh DM. C-terminally truncated forms of Tau, but not full-length Tau or its C-terminal fragments, are released from neurons independently of cell death. J Neurosci. 2015;35(30):10851–65. https://doi.org/10.1523/JNEUROSCI.0387-15.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Karch CM, Jeng AT, Goate AM. Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies. J Biol Chem. 2012;287(51):42751–62. https://doi.org/10.1074/jbc.M112.380642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Katsinelos T, Zeitler M, Dimou E, Karakatsani A, Muller HM, Nachman E, Steringer JP, Ruiz de Almodovar C, Nickel W, Jahn TR. Unconventional secretion mediates the trans-cellular spreading of Tau. Cell Rep. 2018;23(7):2039–55. https://doi.org/10.1016/j.celrep.2018.04.056.

    Article  CAS  PubMed  Google Scholar 

  77. Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J, Sharma AM, Miller TM, Diamond MI. Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron. 2016;92(4):796–812. https://doi.org/10.1016/j.neuron.2016.09.055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI. Trans-cellular propagation of Tau aggregation by fibrillar species. J Biol Chem. 2012;287(23):19440–51. https://doi.org/10.1074/jbc.M112.346072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim D, Lim S, Haque MM, Ryoo N, Hong HS, Rhim H, Lee DE, Chang YT, Lee JS, Cheong E, Kim DJ, Kim YK. Identification of disulfide cross-linked tau dimer responsible for tau propagation. Sci Rep. 2015;5:15231. https://doi.org/10.1038/srep15231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kim W, Lee S, Jung C, Ahmed A, Lee G, Hall GF. Interneuronal transfer of human tau between lamprey central neurons in situ. J Alzheimers Dis. 2010;19(2):647–64. https://doi.org/10.3233/JAD-2010-1273.

    Article  CAS  PubMed  Google Scholar 

  81. Kowal J, Tkach M, Thery C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol. 2014;29:116–25. https://doi.org/10.1016/j.ceb.2014.05.004.

    Article  CAS  PubMed  Google Scholar 

  82. Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Guerrero-Munoz MJ, Kiritoshi T, Neugebauer V, Jackson GR, Kayed R. Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau. Sci Rep. 2012;2:700. https://doi.org/10.1038/srep00700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Lasagna-Reeves CA, Castillo-Carranza DL, Sengupta U, Sarmiento J, Troncoso J, Jackson GR, Kayed R. Identification of oligomers at early stages of tau aggregation in Alzheimer’s disease. FASEB J. 2012;26(5):1946–59. https://doi.org/10.1096/fj.11-199851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci. 2005;25(25):6016–24. https://doi.org/10.1523/JNEUROSCI.0692-05.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Lee S, Kim W, Li Z, Hall GF. Accumulation of vesicle-associated human tau in distal dendrites drives degeneration and tau secretion in an in situ cellular tauopathy model. Int J Alzheimers Dis. 2012;2012:172837. https://doi.org/10.1155/2012/172837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Levarska L, Zilka N, Jadhav S, Neradil P, Novak M. Of rodents and men: the mysterious interneuronal pilgrimage of misfolded protein tau in Alzheimer’s disease. J Alzheimers Dis. 2013;37(3):569–77. https://doi.org/10.3233/JAD-131106.

    Article  CAS  PubMed  Google Scholar 

  87. Liberski PP. Prion, prionoids and infectious amyloid. Parkinsonism Relat Disord. 2014;20(Suppl 1):S80–4. https://doi.org/10.1016/S1353-8020(13)70021-X.

    Article  PubMed  Google Scholar 

  88. Liu L, Drouet V, Wu JW, Witter MP, Small SA, Clelland C, Duff K. Trans-synaptic spread of tau pathology in vivo. PLoS One. 2012;7(2):e31302. https://doi.org/10.1371/journal.pone.0031302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, Lee VM. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949–53. https://doi.org/10.1126/science.1227157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Luk KC, Kehm VM, Zhang B, O’Brien P, Trojanowski JQ, Lee VM. Intracerebral inoculation of pathological alpha-synuclein initiates a rapidly progressive neurodegenerative alpha-synucleinopathy in mice. J Exp Med. 2012;209(5):975–86. https://doi.org/10.1084/jem.20112457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Martini-Stoica H, Cole AL, Swartzlander DB, Chen F, Wan YW, Bajaj L, Bader DA, Lee VMY, Trojanowski JQ, Liu Z, Sardiello M, Zheng H. TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading. J Exp Med. 2018;215(9):2355–77. https://doi.org/10.1084/jem.20172158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Meyer V, Dinkel PD, Rickman Hager E, Margittai M. Amplification of Tau fibrils from minute quantities of seeds. Biochemistry. 2014;53(36):5804–9. https://doi.org/10.1021/bi501050g.

    Article  CAS  PubMed  Google Scholar 

  93. Meyer-Luehmann M, Coomaraswamy J, Bolmont T, Kaeser S, Schaefer C, Kilger E, Neuenschwander A, Abramowski D, Frey P, Jaton AL, Vigouret JM, Paganetti P, Walsh DM, Mathews PM, Ghiso J, Staufenbiel M, Walker LC, Jucker M. Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science. 2006;313(5794):1781–4. https://doi.org/10.1126/science.1131864.

    Article  CAS  PubMed  Google Scholar 

  94. Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P, Mandelkow E, Mandelkow EM, Kaminski CF, Kaminski Schierle GS. Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. J Biol Chem. 2014;289(2):956–67. https://doi.org/10.1074/jbc.M113.515445.

    Article  CAS  PubMed  Google Scholar 

  95. Min SW, Sohn PD, Li Y, Devidze N, Johnson JR, Krogan NJ, Masliah E, Mok SA, Gestwicki JE, Gan L. SIRT1 Deacetylates Tau and reduces pathogenic Tau spread in a mouse model of tauopathy. J Neurosci. 2018;38(15):3680–8. https://doi.org/10.1523/JNEUROSCI.2369-17.2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mirbaha H, Chen D, Morazova OA, Ruff KM, Sharma AM, Liu X, Goodarzi M, Pappu RV, Colby DW, Mirzaei H, Joachimiak LA, Diamond MI. Inert and seed-competent tau monomers suggest structural origins of aggregation. elife. 2018;7 https://doi.org/10.7554/eLife.36584.

  97. Mirbaha H, Holmes BB, Sanders DW, Bieschke J, Diamond MI. Tau trimers are the minimal propagation unit spontaneously internalized to seed intracellular aggregation. J Biol Chem. 2015;290(24):14893–903. https://doi.org/10.1074/jbc.M115.652693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Mohamed NV, Desjardins A, Leclerc N. Tau secretion is correlated to an increase of Golgi dynamics. PLoS One. 2017;12(5):e0178288. https://doi.org/10.1371/journal.pone.0178288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Mohamed NV, Plouffe V, Remillard-Labrosse G, Planel E, Leclerc N. Starvation and inhibition of lysosomal function increased tau secretion by primary cortical neurons. Sci Rep. 2014;4:5715. https://doi.org/10.1038/srep05715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Morales R, Duran-Aniotz C, Castilla J, Estrada LD, Soto C. De novo induction of amyloid-beta deposition in vivo. Mol Psychiatry. 2012;17(12):1347–53. https://doi.org/10.1038/mp.2011.120.

    Article  CAS  PubMed  Google Scholar 

  101. Mougenot AL, Nicot S, Bencsik A, Morignat E, Verchere J, Lakhdar L, Legastelois S, Baron T. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol Aging. 2012;33(9):2225–8. https://doi.org/10.1016/j.neurobiolaging.2011.06.022.

    Article  CAS  PubMed  Google Scholar 

  102. Mudher A, Colin M, Dujardin S, Medina M, Dewachter I, Alavi Naini SM, Mandelkow EM, Mandelkow E, Buee L, Goedert M, Brion JP. What is the evidence that tau pathology spreads through prion-like propagation? Acta Neuropathol Commun. 2017;5(1):99. https://doi.org/10.1186/s40478-017-0488-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Mukrasch MD, Bibow S, Korukottu J, Jeganathan S, Biernat J, Griesinger C, Mandelkow E, Zweckstetter M. Structural polymorphism of 441-residue tau at single residue resolution. PLoS Biol. 2009;7(2):e34. https://doi.org/10.1371/journal.pbio.1000034.

    Article  CAS  PubMed  Google Scholar 

  104. Narasimhan S, Guo JL, Changolkar L, Stieber A, McBride JD, Silva LV, He Z, Zhang B, Gathagan RJ, Trojanowski JQ, Lee VMY. Pathological Tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J Neurosci. 2017;37(47):11406–23. https://doi.org/10.1523/JNEUROSCI.1230-17.2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Nicholls SB, DeVos SL, Commins C, Nobuhara C, Bennett RE, Corjuc DL, Maury E, Eftekharzadeh B, Akingbade O, Fan Z, Roe AD, Takeda S, Wegmann S, Hyman BT. Characterization of TauC3 antibody and demonstration of its potential to block tau propagation. PLoS One. 2017;12(5):e0177914. https://doi.org/10.1371/journal.pone.0177914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Nobuhara CK, DeVos SL, Commins C, Wegmann S, Moore BD, Roe AD, Costantino I, Frosch MP, Pitstick R, Carlson GA, Hock C, Nitsch RM, Montrasio F, Grimm J, Cheung AE, Dunah AW, Wittmann M, Bussiere T, Weinreb PH, Hyman BT, Takeda S. Tau antibody targeting pathological species blocks neuronal uptake and interneuron propagation of Tau in vitro. Am J Pathol. 2017;187(6):1399–412. https://doi.org/10.1016/j.ajpath.2017.01.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M. Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases. J Biol Chem. 2010;285(45):34885–98. https://doi.org/10.1074/jbc.M110.148460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M, Holtta M, Rosen C, Olsson C, Strobel G, Wu E, Dakin K, Petzold M, Blennow K, Zetterberg H. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84. https://doi.org/10.1016/S1474-4422(16)00070-3.

    Article  CAS  PubMed  Google Scholar 

  109. Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R, Giugliano M, Van den Haute C, Melki R, Baekelandt V. Alpha-synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature. 2015;522(7556):340–4. https://doi.org/10.1038/nature14547.

    Article  CAS  PubMed  Google Scholar 

  110. Peeraer E, Bottelbergs A, Van Kolen K, Stancu IC, Vasconcelos B, Mahieu M, Duytschaever H, Ver Donck L, Torremans A, Sluydts E, Van Acker N, Kemp JA, Mercken M, Brunden KR, Trojanowski JQ, Dewachter I, Lee VM, Moechars D. Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice. Neurobiol Dis. 2015;73:83–95. https://doi.org/10.1016/j.nbd.2014.08.032.

    Article  CAS  PubMed  Google Scholar 

  111. Petkova AT, Leapman RD, Guo Z, Yau WM, Mattson MP, Tycko R. Self-propagating, molecular-level polymorphism in Alzheimer’s beta-amyloid fibrils. Science. 2005;307(5707):262–5. https://doi.org/10.1126/science.1105850.

    Article  CAS  PubMed  Google Scholar 

  112. Piacentini R, Li Puma DD, Mainardi M, Lazzarino G, Tavazzi B, Arancio O, Grassi C. Reduced gliotransmitter release from astrocytes mediates tau-induced synaptic dysfunction in cultured hippocampal neurons. Glia. 2017;65(8):1302–16. https://doi.org/10.1002/glia.23163.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Plouffe V, Mohamed NV, Rivest-McGraw J, Bertrand J, Lauzon M, Leclerc N. Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS One. 2012;7(5):e36873. https://doi.org/10.1371/journal.pone.0036873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Polanco JC, Li C, Bodea LG, Martinez-Marmol R, Meunier FA, Gotz J. Amyloid-beta and tau complexity – towards improved biomarkers and targeted therapies. Nat Rev Neurol. 2018;14(1):22–39. https://doi.org/10.1038/nrneurol.2017.162.

    Article  CAS  PubMed  Google Scholar 

  115. Polydoro M, Dzhala VI, Pooler AM, Nicholls SB, McKinney AP, Sanchez L, Pitstick R, Carlson GA, Staley KJ, Spires-Jones TL, Hyman BT. Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer’s disease model. Acta Neuropathol. 2014;127(2):257–70. https://doi.org/10.1007/s00401-013-1215-5.

    Article  CAS  PubMed  Google Scholar 

  116. Pooler AM, Phillips EC, Lau DH, Noble W, Hanger DP. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep. 2013;14(4):389–94. https://doi.org/10.1038/embor.2013.15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Pooler AM, Polydoro M, Maury EA, Nicholls SB, Reddy SM, Wegmann S, William C, Saqran L, Cagsal-Getkin O, Pitstick R, Beier DR, Carlson GA, Spires-Jones TL, Hyman BT. Amyloid accelerates tau propagation and toxicity in a model of early Alzheimer’s disease. Acta Neuropathol Commun. 2015;3:14. https://doi.org/10.1186/s40478-015-0199-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Probst A, Tolnay M, Langui D, Goedert M, Spillantini MG. Pick’s disease: hyperphosphorylated tau protein segregates to the somatoaxonal compartment. Acta Neuropathol. 1996;92(6):588–96.

    Article  CAS  PubMed  Google Scholar 

  119. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982;216(4542):136–44.

    Article  CAS  PubMed  Google Scholar 

  120. Rajendran L, Bali J, Barr MM, Court FA, Kramer-Albers EM, Picou F, Raposo G, van der Vos KE, van Niel G, Wang J, Breakefield XO. Emerging roles of extracellular vesicles in the nervous system. J Neurosci. 2014;34(46):15482–9. https://doi.org/10.1523/JNEUROSCI.3258-14.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K. Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A. 2006;103(30):11172–7. https://doi.org/10.1073/pnas.0603838103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Rauch JN, Chen JJ, Sorum AW, Miller GM, Sharf T, See SK, Hsieh-Wilson LC, Kampmann M, Kosik KS. Tau internalization is regulated by 6-O sulfation on heparan sulfate proteoglycans (HSPGs). Sci Rep. 2018;8(1):6382. https://doi.org/10.1038/s41598-018-24904-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Rebeck GW, Hyman BT. Neuroanatomical connections and specific regional vulnerability in Alzheimer’s disease. Neurobiol Aging. 1993;14(1):45–7; discussion 55-46

    Article  CAS  PubMed  Google Scholar 

  124. Reilly P, Winston CN, Baron KR, Trejo M, Rockenstein EM, Akers JC, Kfoury N, Diamond M, Masliah E, Rissman RA, Yuan SH. Novel human neuronal tau model exhibiting neurofibrillary tangles and transcellular propagation. Neurobiol Dis. 2017;106:222–34. https://doi.org/10.1016/j.nbd.2017.06.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Rodriguez L, Mohamed NV, Desjardins A, Lippe R, Fon EA, Leclerc N. Rab7A regulates tau secretion. J Neurochem. 2017;141(4):592–605. https://doi.org/10.1111/jnc.13994.

    Article  CAS  PubMed  Google Scholar 

  126. Saito Y, Ruberu NN, Sawabe M, Arai T, Tanaka N, Kakuta Y, Yamanouchi H, Murayama S. Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol. 2004;63(9):911–8.

    Article  PubMed  Google Scholar 

  127. Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, Jackson B, McKee AC, Alvarez VE, Lee NC, Hall GF. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem. 2012;287(6):3842–9. https://doi.org/10.1074/jbc.M111.277061.

    Article  CAS  PubMed  Google Scholar 

  128. Sanders DW, Kaufman SK, DeVos SL, Sharma AM, Mirbaha H, Li A, Barker SJ, Foley AC, Thorpe JR, Serpell LC, Miller TM, Grinberg LT, Seeley WW, Diamond MI. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron. 2014;82(6):1271–88. https://doi.org/10.1016/j.neuron.2014.04.047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Santa-Maria I, Varghese M, Ksiezak-Reding H, Dzhun A, Wang J, Pasinetti GM. Paired helical filaments from Alzheimer disease brain induce intracellular accumulation of Tau protein in aggresomes. J Biol Chem. 2012;287(24):20522–33. https://doi.org/10.1074/jbc.M111.323279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH. Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005;309(5733):476–81. https://doi.org/10.1126/science.1113694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Schwarz AJ, Yu P, Miller BB, Shcherbinin S, Dickson J, Navitsky M, Joshi AD, Devous MD Sr, Mintun MS. Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. Brain. 2016;139(Pt 5):1539–50. https://doi.org/10.1093/brain/aww023.

    Article  PubMed  Google Scholar 

  132. Sepulcre J, Grothe MJ, d’Oleire Uquillas F, Ortiz-Teran L, Diez I, Yang HS, Jacobs HIL, Hanseeuw BJ, Li Q, El-Fakhri G, Sperling RA, Johnson KA. Neurogenetic contributions to amyloid beta and tau spreading in the human cortex. Nat Med. 2018; https://doi.org/10.1038/s41591-018-0206-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Silva JM, Rodrigues S, Sampaio-Marques B, Gomes P, Neves-Carvalho A, Dioli C, Soares-Cunha C, Mazuik BF, Takashima A, Ludovico P, Wolozin B, Sousa N, Sotiropoulos I. Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology. Cell Death Differ. 2018; https://doi.org/10.1038/s41418-018-0217-1.

    Article  Google Scholar 

  134. Simon D, Garcia-Garcia E, Royo F, Falcon-Perez JM, Avila J. Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS Lett. 2012;586(1):47–54. https://doi.org/10.1016/j.febslet.2011.11.022.

    Article  CAS  PubMed  Google Scholar 

  135. Smolek T, Jadhav S, Brezovakova V, Cubinkova V, Valachova B, Novak P, Zilka N. First-in-rat study of human Alzheimer’s disease Tau propagation. Mol Neurobiol. 2018; https://doi.org/10.1007/s12035-018-1102-0.

    Article  PubMed  Google Scholar 

  136. Sokolow S, Henkins KM, Bilousova T, Gonzalez B, Vinters HV, Miller CA, Cornwell L, Poon WW, Gylys KH. Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer’s disease. J Neurochem. 2015;133(3):368–79. https://doi.org/10.1111/jnc.12991.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau Q, Davis DM. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol. 2008;10(2):211–9. https://doi.org/10.1038/ncb1682.

    Article  CAS  PubMed  Google Scholar 

  138. Stancu IC, Vasconcelos B, Ris L, Wang P, Villers A, Peeraer E, Buist A, Terwel D, Baatsen P, Oyelami T, Pierrot N, Casteels C, Bormans G, Kienlen-Campard P, Octave JN, Moechars D, Dewachter I. Templated misfolding of Tau by prion-like seeding along neuronal connections impairs neuronal network function and associated behavioral outcomes in Tau transgenic mice. Acta Neuropathol. 2015;129(6):875–94. https://doi.org/10.1007/s00401-015-1413-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Stohr J, Watts JC, Mensinger ZL, Oehler A, Grillo SK, DeArmond SJ, Prusiner SB, Giles K. Purified and synthetic Alzheimer’s amyloid beta (Abeta) prions. Proc Natl Acad Sci U S A. 2012;109(27):11025–30. https://doi.org/10.1073/pnas.1206555109.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Stopschinski BE, Holmes BB, Miller GM, Manon VA, Vaquer-Alicea J, Prueitt WL, Hsieh-Wilson LC, Diamond MI. Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus alpha-synuclein and beta-amyloid aggregates. J Biol Chem. 2018;293(27):10826–40. https://doi.org/10.1074/jbc.RA117.000378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Takahashi M, Miyata H, Kametani F, Nonaka T, Akiyama H, Hisanaga S, Hasegawa M. Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau. Acta Neuropathol. 2015;129(6):895–907. https://doi.org/10.1007/s00401-015-1415-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Takeda S, Wegmann S, Cho H, DeVos SL, Commins C, Roe AD, Nicholls SB, Carlson GA, Pitstick R, Nobuhara CK, Costantino I, Frosch MP, Muller DJ, Irimia D, Hyman BT. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer’s disease brain. Nat Commun. 2015;6:8490. https://doi.org/10.1038/ncomms9490.

    Article  CAS  PubMed  Google Scholar 

  143. Tang Z, Ioja E, Bereczki E, Hultenby K, Li C, Guan Z, Winblad B, Pei JJ. mTor mediates tau localization and secretion: implication for Alzheimer’s disease. Biochim Biophys Acta. 2015;1853(7):1646–57. https://doi.org/10.1016/j.bbamcr.2015.03.003.

    Article  CAS  PubMed  Google Scholar 

  144. Tardivel M, Begard S, Bousset L, Dujardin S, Coens A, Melki R, Buee L, Colin M. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies. Acta Neuropathol Commun. 2016;4(1):117. https://doi.org/10.1186/s40478-016-0386-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Telling GC, Parchi P, DeArmond SJ, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, Prusiner SB. Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating prion diversity. Science. 1996;274(5295):2079–82.

    Article  CAS  PubMed  Google Scholar 

  146. Usenovic M, Niroomand S, Drolet RE, Yao L, Gaspar RC, Hatcher NG, Schachter J, Renger JJ, Parmentier-Batteur S. Internalized Tau oligomers cause neurodegeneration by inducing accumulation of pathogenic Tau in human neurons derived from induced pluripotent stem cells. J Neurosci. 2015;35(42):14234–50. https://doi.org/10.1523/JNEUROSCI.1523-15.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Varghese M, Santa-Maria I, Ho L, Ward L, Yemul S, Dubner L, Ksiezak-Reding H, Pasinetti GM. Extracellular Tau paired helical filaments differentially affect Tau pathogenic mechanisms in mitotic and post-mitotic cells: implications for mechanisms of Tau propagation in the brain. J Alzheimers Dis. 2016;54(2):477–96. https://doi.org/10.3233/JAD-160166.

    Article  CAS  PubMed  Google Scholar 

  148. Vasconcelos B, Stancu IC, Buist A, Bird M, Wang P, Vanoosthuyse A, Van Kolen K, Verheyen A, Kienlen-Campard P, Octave JN, Baatsen P, Moechars D, Dewachter I. Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo. Acta Neuropathol. 2016;131(4):549–69. https://doi.org/10.1007/s00401-015-1525-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Verny M, Jellinger KA, Hauw JJ, Bancher C, Litvan I, Agid Y. Progressive supranuclear palsy: a clinicopathological study of 21 cases. Acta Neuropathol. 1996;91(4):427–31.

    Article  CAS  PubMed  Google Scholar 

  150. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, Meaney DF, Trojanowski JQ, Lee VM. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron. 2011;72(1):57–71. https://doi.org/10.1016/j.neuron.2011.08.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Walker LC, Levine H 3rd, Mattson MP, Jucker M. Inducible proteopathies. Trends Neurosci. 2006;29(8):438–43. https://doi.org/10.1016/j.tins.2006.06.010.

    Article  CAS  PubMed  Google Scholar 

  152. Wang Y, Balaji V, Kaniyappan S, Kruger L, Irsen S, Tepper K, Chandupatla R, Maetzler W, Schneider A, Mandelkow E, Mandelkow EM. The release and trans-synaptic transmission of Tau via exosomes. Mol Neurodegener. 2017;12(1):5. https://doi.org/10.1186/s13024-016-0143-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Wegmann S, Bennett RE, Amaral AS, Hyman BT. Studying tau protein propagation and pathology in the mouse brain using adeno-associated viruses. Methods Cell Biol. 2017;141:307–22. https://doi.org/10.1016/bs.mcb.2017.06.014.

    Article  PubMed  Google Scholar 

  154. Wegmann S, Maury EA, Kirk MJ, Saqran L, Roe A, DeVos SL, Nicholls S, Fan Z, Takeda S, Cagsal-Getkin O, William CM, Spires-Jones TL, Pitstick R, Carlson GA, Pooler AM, Hyman BT. Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J. 2015;34(24):3028–41. https://doi.org/10.15252/embj.201592748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Williams DR, Holton JL, Strand C, Pittman A, de Silva R, Lees AJ, Revesz T. Pathological tau burden and distribution distinguishes progressive supranuclear palsy-parkinsonism from Richardson’s syndrome. Brain. 2007;130(Pt 6):1566–76. https://doi.org/10.1093/brain/awm104.

    Article  PubMed  Google Scholar 

  156. Woerman AL, Aoyagi A, Patel S, Kazmi SA, Lobach I, Grinberg LT, McKee AC, Seeley WW, Olson SH, Prusiner SB. Tau prions from Alzheimer’s disease and chronic traumatic encephalopathy patients propagate in cultured cells. Proc Natl Acad Sci U S A. 2016;113(50):E8187–96. https://doi.org/10.1073/pnas.1616344113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Wu JW, Herman M, Liu L, Simoes S, Acker CM, Figueroa H, Steinberg JI, Margittai M, Kayed R, Zurzolo C, Di Paolo G, Duff KE. Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J Biol Chem. 2013;288(3):1856–70. https://doi.org/10.1074/jbc.M112.394528.

    Article  CAS  PubMed  Google Scholar 

  158. Wu JW, Hussaini SA, Bastille IM, Rodriguez GA, Mrejeru A, Rilett K, Sanders DW, Cook C, Fu H, Boonen RA, Herman M, Nahmani E, Emrani S, Figueroa YH, Diamond MI, Clelland CL, Wray S, Duff KE. Neuronal activity enhances tau propagation and tau pathology in vivo. Nat Neurosci. 2016;19(8):1085–92. https://doi.org/10.1038/nn.4328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE, Jiang H, Cirrito JR, Patel TK, Hochgrafe K, Mandelkow EM, Holtzman DM. Neuronal activity regulates extracellular tau in vivo. J Exp Med. 2014;211(3):387–93. https://doi.org/10.1084/jem.20131685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron. 2013;80(2):402–14. https://doi.org/10.1016/j.neuron.2013.07.046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Yonetani M, Nonaka T, Masuda M, Inukai Y, Oikawa T, Hisanaga S, Hasegawa M. Conversion of wild-type alpha-synuclein into mutant-type fibrils and its propagation in the presence of A30P mutant. J Biol Chem. 2009;284(12):7940–50. https://doi.org/10.1074/jbc.M807482200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Yuyama K, Yamamoto N, Yanagisawa K. Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation. J Neurochem. 2008;105(1):217–24. https://doi.org/10.1111/j.1471-4159.2007.05128.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA

    Simon Dujardin & Bradley T. Hyman

Authors
  1. Simon Dujardin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley T. Hyman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bradley T. Hyman .

Editor information

Editors and Affiliations

  1. Department of Life Sciences, Gakushuin University, Tokyo, Japan

    Akihiko Takashima

  2. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. University of Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Luc Buee

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dujardin, S., Hyman, B.T. (2019). Tau Prion-Like Propagation: State of the Art and Current Challenges. In: Takashima, A., Wolozin, B., Buee, L. (eds) Tau Biology. Advances in Experimental Medicine and Biology, vol 1184. Springer, Singapore. https://doi.org/10.1007/978-981-32-9358-8_23

Download citation

Publish with us

Policies and ethics

Search

Navigation