1932

Abstract

Most common neurodegenerative diseases feature deposition of protein amyloids and degeneration of brain networks. Amyloids are ordered protein assemblies that can act as templates for their own replication through monomer addition. Evidence suggests that this characteristic may underlie the progression of pathology in neurodegenerative diseases. Many different amyloid proteins, including Aβ, tau, and α-synuclein, exhibit properties similar to those of infectious prion protein in experimental systems: discrete and self-replicating amyloid structures, transcellular propagation of aggregation, and transmissible neuropathology. This review discusses the contribution of prion phenomena and transcellular propagation to the progression of pathology in common neurodegenerative diseases such as Alzheimer's and Parkinson's. It reviews fundamental events such as cell entry, amplification, and transcellular movement. It also discusses amyloid strains, which produce distinct patterns of neuropathology and spread through the nervous system. These concepts may impact the development of new diagnostic and therapeutic strategies.

Keyword(s): aggregationamyloidprionpropagationstraintau
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2019-06-20
2024-06-25
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Literature Cited

  1. 1. 
    Eisenberg DS, Sawaya MR. 2017. Structural studies of amyloid proteins at the molecular level. Annu. Rev. Biochem. 86:69–95
    [Google Scholar]
  2. 2. 
    Knowles TPJ, Vendruscolo M, Dobson CM 2014. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15:6384–96
    [Google Scholar]
  3. 3. 
    Dobson CM. 2017. The amyloid phenomenon and its links with human disease. Cold Spring Harb. Perspect. Biol. 9:6a023648–15
    [Google Scholar]
  4. 4. 
    Chiti F, Dobson CM. 2017. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu. Rev. Biochem. 86:27–68
    [Google Scholar]
  5. 5. 
    Jarrett JT, Lansbury PT Jr 1993. Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie?. Cell 73:1055–58
    [Google Scholar]
  6. 6. 
    Harper JD, Lansbury PT Jr 1997. Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem. 66:385–407
    [Google Scholar]
  7. 7. 
    Collins SR, Douglass A, Vale RD, Weissman JS 2004. Mechanism of prion propagation: amyloid growth occurs by monomer addition. PLOS Biol 2:10e321–29
    [Google Scholar]
  8. 8. 
    Powers ET, Powers DL. 2006. The kinetics of nucleated polymerizations at high concentrations: amyloid fibril formation near and above the “supercritical concentration. .” Biophys. J. 91:122–32
    [Google Scholar]
  9. 9. 
    Mirbaha H, Chen D, Morazova OA, Ruff KM, Sharma AM et al. 2018. Inert and seed-competent tau monomers suggest structural origins of aggregation. eLife 7:e36584
    [Google Scholar]
  10. 10. 
    Labbadia J, Morimoto RI. 2015. The biology of proteostasis in aging and disease. Annu. Rev. Biochem. 84:435–64
    [Google Scholar]
  11. 11. 
    Kundra R, Ciryam P, Morimoto RI, Dobson CM, Vendruscolo M 2017. Protein homeostasis of a metastable subproteome associated with Alzheimer's disease. PNAS 114:28E5703–11
    [Google Scholar]
  12. 12. 
    Prusiner SB. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216:4542136–44
    [Google Scholar]
  13. 13. 
    Bolton D, McKinley M, Prusiner S 1982. Identification of a protein that purifies with the scrapie prion. Science 218:45791309–11
    [Google Scholar]
  14. 14. 
    Pan K-M, Baldwin M, Nguyen J, Gasset M, Serban A et al. 1993. Conversion of α-helices into, β-sheets features in the formation of the scrapie prion proteins. PNAS 90:10962–66
    [Google Scholar]
  15. 15. 
    Sanders DW, Kaufman SK, DeVos SL, Sharma AM, Mirbaha H et al. 2014. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82:61271–88
    [Google Scholar]
  16. 16. 
    Sanders DW, Kaufman SK, Holmes BB, Diamond MI 2016. Prions and protein assemblies that convey biological information in health and disease. Neuron 89:3433–48
    [Google Scholar]
  17. 17. 
    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. 11:7909–13
    [Google Scholar]
  18. 18. 
    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 313:57941781–84
    [Google Scholar]
  19. 19. 
    Desplats P, Lee H-J, Bae E-J, Patrick C, Rockenstein E et al. 2009. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein. PNAS 106:3113010–15
    [Google Scholar]
  20. 20. 
    Li J-Y, Englund E, Holton JL, Soulet D, Hagell P et al. 2008. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med. 14:5501–3
    [Google Scholar]
  21. 21. 
    Frost B, Jacks RL, Diamond MI 2009. Propagation of tau misfolding from the outside to the inside of a cell. J. Biol. Chem. 284:1912845–52
    [Google Scholar]
  22. 22. 
    Fraser H, Dickinson AG. 1985. Targeting of scrapie lesions and spread of agent via the retino-tectal projection. Brain Res 346:32–41
    [Google Scholar]
  23. 23. 
    Scott JR, Foster JD, Fraser H 1993. Conjunctival instillation of scrapie in mice can produce disease. Vet. Microbiol. 34:4305–9
    [Google Scholar]
  24. 24. 
    Brandner S, Raeber A, Sailer A, Blattler T, Fischer M et al. 1996. Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system. PNAS 93:2313148–51
    [Google Scholar]
  25. 25. 
    Kane MD, Lipinski WJ, Callahan MJ, Bian F, Durham RA et al. 2000. Evidence for seeding of β-amyloid by intracerebral infusion of Alzheimer brain extracts in β-amyloid precursor protein-transgenic mice. J. Neurosci. 20:103606–11
    [Google Scholar]
  26. 26. 
    Walker LC, Callahan MJ, Bian F, Durham RA, Roher AE, Lipinski WJ 2002. Exogenous induction of cerebral β-amyloidosis in βAPP-transgenic mice. Peptides 23:71241–47
    [Google Scholar]
  27. 27. 
    Petkova AT, Leapman RD, Guo Z, Yau W-M, Mattson MP, Tycko R 2005. Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils. Science 307:5707262–65
    [Google Scholar]
  28. 28. 
    Eisele YS, Bolmont T, Heikenwalder M, Langer F, Jacobson LH et al. 2009. Induction of cerebral β-amyloidosis: intracerebral versus systemic Aβ inoculation. PNAS 106:3112926–31
    [Google Scholar]
  29. 29. 
    Eisele YS, Obermüller U, Heilbronner G, Baumann F, Kaeser SA et al. 2010. Peripherally applied Aβ-containing inoculates induce cerebral β-amyloidosis. Science 330:6006980–82
    [Google Scholar]
  30. 30. 
    Lu J-X, Qiang W, Yau W-M, Schwieters CD, Meredith SC, Tycko R 2013. Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue. Cell 154:61257–68
    [Google Scholar]
  31. 31. 
    Heilbronner G, Eisele YS, Langer F, Kaeser SA, Novotny R et al. 2013. Seeded strain-like transmission of β-amyloid morphotypes in APP transgenic mice. EMBO Rep 14:111017–22
    [Google Scholar]
  32. 32. 
    Prusiner SB. 1984. Some speculations about prions, amyloid, and Alzheimer's disease. N. Engl. J. Med. 310:10661–63
    [Google Scholar]
  33. 33. 
    Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW 2008. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat. Med. 14:5504–6
    [Google Scholar]
  34. 34. 
    Luk KC, Song C, O'Brien P, Stieber A, Branch JR et al. 2009. Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. PNAS 106:4720051–56
    [Google Scholar]
  35. 35. 
    Ren P-H, Lauckner JE, Kachirskaia I, Heuser JE, Melki R, Kopito RR 2009. Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat. Cell Biol. 11:2219–25
    [Google Scholar]
  36. 36. 
    Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M 2010. Seeded aggregation and toxicity of α-synuclein and tau: cellular models of neurodegenerative diseases. J. Biol. Chem. 285:4534885–98
    [Google Scholar]
  37. 37. 
    Münch C, O'Brien J, Bertolotti A 2011. Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells. PNAS 108:93548–53
    [Google Scholar]
  38. 38. 
    Grad LI, Guest WC, Yanai A, Pokrishevsky E, O'Neill MA et al. 2011. Intermolecular transmission of superoxide dismutase 1 misfolding in living cells. PNAS 108:3916398–403
    [Google Scholar]
  39. 39. 
    Nonaka T, Masuda-Suzukake M, Arai T, Hasegawa Y, Akatsu H et al. 2013. Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep 4:1124–34
    [Google Scholar]
  40. 40. 
    Walsh DM, Selkoe DJ. 2016. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat. Rev. Neurosci. 17:4251–60
    [Google Scholar]
  41. 41. 
    Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI 2012. Trans-cellular propagation of Tau aggregation by fibrillar species. J. Biol. Chem. 287:2319440–51
    [Google Scholar]
  42. 42. 
    Guo JL, Lee VM-Y. 2011. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J. Biol. Chem. 286:1715317–31
    [Google Scholar]
  43. 43. 
    de Calignon A, Polydoro M, Suárez-Calvet M, William C, Adamowicz DH et al. 2012. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73:4685–97
    [Google Scholar]
  44. 44. 
    Iba M, Guo JL, McBride JD, Zhang B, Trojanowski JQ, Lee VM-Y 2013. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy. J. Neurosci. 33:31024–37
    [Google Scholar]
  45. 45. 
    Liu L, Drouet V, Wu JW, Witter MP, Small SA et al. 2012. Trans-synaptic spread of tau pathology in vivo. PLOS ONE 7:2e31302
    [Google Scholar]
  46. 46. 
    Bahr BA, Hoffman KB, Yang AJ, Hess US, Glabe CG, Lynch G 1998. Amyloid β protein is internalized selectively by hippocampal field CA1 and causes neurons to accumulate amyloidogenic carboxyterminal fragments of the amyloid precursor protein. J. Comp. Neurol. 397:139–47
    [Google Scholar]
  47. 47. 
    Nath S, Agholme L, Kurudenkandy FR, Granseth B, Marcusson J, Hallbeck M 2012. Spreading of neurodegenerative pathology via neuron-to-neuron transmission of β-amyloid. J. Neurosci. 32:268767–77
    [Google Scholar]
  48. 48. 
    Jaunmuktane Z, Mead S, Ellis M, Wadsworth JDF, Nicoll AJ et al. 2015. Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. Nature 525:7568247–50
    [Google Scholar]
  49. 49. 
    Hansen C, Angot E, Bergström A-L, Steiner JA, Pieri L et al. 2011. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J. Clin. Investig. 121:2715–25
    [Google Scholar]
  50. 50. 
    Freundt EC, Maynard N, Clancy EK, Roy S, Bousset L et al. 2012. Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport. Ann. Neurol. 72:4517–24
    [Google Scholar]
  51. 51. 
    Luk KC, Kehm VM, Zhang B, O'Brien P, Trojanowski JQ, Lee VM-Y 2012. Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice. J. Exp. Med. 209:5975–86
    [Google Scholar]
  52. 52. 
    Luk KC, Kehm V, Carroll J, Zhang Bin, O'Brien P et al. 2012. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:6109949–53
    [Google Scholar]
  53. 53. 
    Pokrishevsky E, Grad LI, Cashman NR 2016. TDP-43 or FUS-induced misfolded human wild-type SOD1 can propagate intercellularly in a prion-like fashion. Sci. Rep. 6:122155
    [Google Scholar]
  54. 54. 
    Ayers JI, Fromholt S, Koch M, DeBosier A, McMahon B et al. 2014. Experimental transmissibility of mutant SOD1 motor neuron disease. Acta Neuropathol 128:6791–803
    [Google Scholar]
  55. 55. 
    Ayers JI, Fromholt SE, O'Neal VM, Diamond JH, Borchelt DR 2016. Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways. Acta Neuropathol 131:1103–14
    [Google Scholar]
  56. 56. 
    Kanu N, Imokawa Y, Drechsel DN, Williamson RA, Birkett CR et al. 2002. Transfer of scrapie prion infectivity by cell contact in culture. Curr. Biol. 12:7523–30
    [Google Scholar]
  57. 57. 
    Magalhães AC, Baron GS, Lee KS, Steele-Mortimer O, Dorward D et al. 2005. Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells. J. Neurosci. 25:215207–16
    [Google Scholar]
  58. 58. 
    Chandler RL. 1961. Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet 1:71911378–79
    [Google Scholar]
  59. 59. 
    Makarava N, Kovacs GG, Bocharova O, Savtchenko R, Alexeeva I et al. 2010. Recombinant prion protein induces a new transmissible prion disease in wild-type animals. Acta Neuropathol 119:2177–87
    [Google Scholar]
  60. 60. 
    Duffy P, Wolf J, Collins G, DeVoe AG, Streeten B, Cowen D 1974. Letter: possible person-to-person transmission of Creutzfeldt-Jakob disease. N. Engl. J. Med. 290:12692–93
    [Google Scholar]
  61. 61. 
    Bernoulli C, Siegfried J, Baumgartner G, Regli F, Rabinowicz T et al. 1977. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1:8009478–79
    [Google Scholar]
  62. 62. 
    Trevino RS, Lauckner JE, Sourigues Y, Pearce MM, Bousset L et al. 2012. Fibrillar structure and charge determine the interaction of polyglutamine protein aggregates with the cell surface. J. Biol. Chem. 287:3529722–28
    [Google Scholar]
  63. 63. 
    Jeon I, Cicchetti F, Cisbani G, Lee S, Li E et al. 2016. Human-to-mouse prion-like propagation of mutant huntingtin protein. Acta Neuropathol 132:4577–92
    [Google Scholar]
  64. 64. 
    Cicchetti F, Lacroix S, Cisbani G, Vallières N, Saint-Pierre M et al. 2014. Mutant huntingtin is present in neuronal grafts in Huntington disease patients. Ann. Neurol. 76:131–42
    [Google Scholar]
  65. 65. 
    Sung JY, Kim J, Paik SR, Park JH, Ahn YS, Chung KC 2001. Induction of neuronal cell death by Rab5A-dependent endocytosis of α-synuclein. J. Biol. Chem. 276:2927441–48
    [Google Scholar]
  66. 66. 
    Liu J, Zhou Y, Wang Y, Fong H, Murray TM, Zhang J 2007. Identification of proteins involved in microglial endocytosis of α-synuclein. J. Proteome Res. 6:93614–27
    [Google Scholar]
  67. 67. 
    Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X et al. 2016. Pathological-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 353:6307aah3374
    [Google Scholar]
  68. 68. 
    Kanekiyo T, Zhang J, Liu Q, Liu CC, Zhang L, Bu G 2011. Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-β uptake. J. Neurosci. 31:51644–51
    [Google Scholar]
  69. 69. 
    Omtri RS, Davidson MW, Arumugam B, Poduslo JF, Kandimalla KK 2012. Differences in the cellular uptake and intracellular itineraries of amyloid beta proteins 40 and 42: ramifications for the Alzheimer's drug discovery. Mol. Pharm. 9:71887–97
    [Google Scholar]
  70. 70. 
    Clifford PM, Siu G, Kosciuk M, Levin EC, Venkataraman V et al. 2008. α7 nicotinic acetylcholine receptor expression by vascular smooth muscle cells facilitates the deposition of Aβ peptides and promotes cerebrovascular amyloid angiopathy. Brain Res 1234:158–71
    [Google Scholar]
  71. 71. 
    Lilja AM, Porras O, Storelli E, Nordberg A, Marutle A 2011. Functional interactions of fibrillar and oligomeric amyloid-β with alpha7 nicotinic receptors in Alzheimer's disease. J. Alzheimers Dis. 23:2335–47
    [Google Scholar]
  72. 72. 
    Bi X, Gall CM, Zhou J, Lynch G 2002. Uptake and pathogenic effects of amyloid beta peptide 1–42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists. Neuroscience 112:4827–40
    [Google Scholar]
  73. 73. 
    Fuentealba RA, Liu Q, Zhang J, Kanekiyo T, Hu X et al. 2010. Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Aβ42 uptake and lysosomal trafficking. PLOS ONE 5:7e11884
    [Google Scholar]
  74. 74. 
    LaFerla FM, Troncoso JC, Strickland DK, Kawas CH, Jay G 1997. Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Aβ stabilization. J. Clin. Investig. 100:2310–20
    [Google Scholar]
  75. 75. 
    Takamura A, Sato Y, Watabe D, Okamoto Y, Nakata T et al. 2012. Sortilin is required for toxic action of Aβ oligomers (AβOs): Extracellular AβOs trigger apoptosis, and intraneuronal AβOs impair degradation pathways. Life Sci 91:23–241177–86
    [Google Scholar]
  76. 76. 
    Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM 2009. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature 457:1128–32
    [Google Scholar]
  77. 77. 
    Wang Y, Cui J, Sun X, Zhang Y 2011. Tunneling-nanotube development in astrocytes depends on p53 activation. Cell Death Differ 18:4732–42
    [Google Scholar]
  78. 78. 
    Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R et al. 2013. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. PNAS 110:33E3138–47
    [Google Scholar]
  79. 79. 
    Stopschinski BE, Holmes BB, Miller GM, Manon VA, Vaquer-Alicea J et al. 2018. Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus α-synuclein and β-amyloid aggregates. J. Biol. Chem. 293:10826–40
    [Google Scholar]
  80. 80. 
    Bernfield M, Götte M, Park PW, Reizes O, Fitzgerald ML et al. 1999. Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68:729–77
    [Google Scholar]
  81. 81. 
    Dujardin S, Bégard S, Caillierez R, Lachaud C, Delattre L et al. 2014. Ectosomes: a new mechanism for non-exosomal secretion of tau protein. PLOS ONE 9:6e100760
    [Google Scholar]
  82. 82. 
    Saman S, Kim W, Raya M, Visnick Y, Miro S et al. 2012. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J. Biol. Chem. 287:63842–49
    [Google Scholar]
  83. 83. 
    Wu JW, Herman M, Liu L, Simoes S, Acker CM et al. 2013. Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons. J. Biol. Chem. 288:31856–70
    [Google Scholar]
  84. 84. 
    Mirbaha H, Holmes BB, Sanders DW, Bieschke J, Diamond MI 2015. Tau trimers are the minimal propagation unit spontaneously internalized to seed intracellular aggregation. J. Biol. Chem. 290:2414893–903
    [Google Scholar]
  85. 85. 
    Bellinger-Kawahara CG, Kempner E, Groth D, Gabizon R, Prusiner SB 1988. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da. Virology 164:2537–41
    [Google Scholar]
  86. 86. 
    Scott JR, Davies D, Fraser H 1992. Scrapie in the central nervous system: neuroanatomical spread of infection and Sinc control of pathogenesis. J. Gen. Virol. 73:71637–44
    [Google Scholar]
  87. 87. 
    Lee S, Kim W, Li Z, Hall GF 2012. 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. 2012:172837
    [Google Scholar]
  88. 88. 
    Karch CM, Jeng AT, Goate AM 2012. Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies. J. Biol. Chem. 287:5142751–62
    [Google Scholar]
  89. 89. 
    Michel CH, Kumar S, Pinotsi D, Tunnacliffe A, St George-Hyslop P et al. 2014. Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. J. Biol. Chem. 289:2956–67
    [Google Scholar]
  90. 90. 
    Chai X, Dage JL, Citron M 2012. Constitutive secretion of tau protein by an unconventional mechanism. Neurobiol. Dis. 48:3356–66
    [Google Scholar]
  91. 91. 
    Pooler AM, Phillips EC, Lau DHW, Noble W, Hanger DP 2013. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 14:4389–94
    [Google Scholar]
  92. 92. 
    Kim W, Lee S, Jung C, Ahmed A, Lee G, Hall GF 2010. Interneuronal transfer of human tau between Lamprey central neurons in situ. J. Alzheimers Dis. 19:2647–64
    [Google Scholar]
  93. 93. 
    Plouffe V, Mohamed N-V, Rivest-McGraw J, Bertrand J, Lauzon M, Leclerc N 2012. Hyperphos-phorylation and cleavage at D421 enhance tau secretion. PLOS ONE 7:5e36873
    [Google Scholar]
  94. 94. 
    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]
  95. 95. 
    Tyson T, Steiner JA, Brundin P 2016. Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J. Neurochem. 139:Suppl. 1275–89
    [Google Scholar]
  96. 96. 
    Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE et al. 2014. Neuronal activity regulates extracellular tau in vivo. J. Exp. Med. 211:3387–93
    [Google Scholar]
  97. 97. 
    Calafate S, Buist A, Miskiewicz K, Vijayan V, Daneels G et al. 2015. Synaptic contacts enhance cell-to-cell tau pathology propagation. Cell Rep 11:81176–83
    [Google Scholar]
  98. 98. 
    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. 19:81085–92
    [Google Scholar]
  99. 99. 
    Funk KE, Mirbaha H, Jiang H, Holtzman DM, Diamond MI 2015. Distinct therapeutic mechanisms of tau antibodies: promoting microglial clearance versus blocking neuronal uptake. J. Biol. Chem. 290:3521652–62
    [Google Scholar]
  100. 100. 
    Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S et al. 2013. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80:2402–14
    [Google Scholar]
  101. 101. 
    Panza F, Solfrizzi V, Seripa D, Imbimbo BP, Lozupone M et al. 2016. Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy. Immunotherapy 8:91119–34
    [Google Scholar]
  102. 102. 
    Takamori S, Holt M, Stenius K, Lemke EA, Grønborg M et al. 2006. Molecular anatomy of a trafficking organelle. Cell 127:4831–46
    [Google Scholar]
  103. 103. 
    Zanusso G, Monaco S, Pocchiari M, Caughey B 2016. Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease. Nat. Rev. Neurol. 12:6325–33
    [Google Scholar]
  104. 104. 
    Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG et al. 2014. A test for Creutzfeldt-Jakob disease using nasal brushings. N. Engl. J. Med. 371:6519–29
    [Google Scholar]
  105. 105. 
    Saijo E, Ghetti B, Zanusso G, Oblak A, Furman JL et al. 2017. Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid. Acta Neuropathol 133:5751–65
    [Google Scholar]
  106. 106. 
    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 52:406960–67
    [Google Scholar]
  107. 107. 
    Meyer V, Dinkel PD, Hager ER, Margittai M 2014. Amplification of tau fibrils from minute quantities of seeds. Biochemistry 53:365804–9
    [Google Scholar]
  108. 108. 
    Salvadores N, Shahnawaz M, Scarpini E, Tagliavini F, Soto C 2014. Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer's disease. Cell Rep 7:1261–68
    [Google Scholar]
  109. 109. 
    Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J et al. 2016. Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann. Clin. Transl. Neurol. 3:10812–18
    [Google Scholar]
  110. 110. 
    Holmes BB, Furman JL, Mahan TE, Yamasaki TR, Mirbaha H et al. 2014. Proteopathic tau seeding predicts tauopathy in vivo. PNAS 111:41E4376–85
    [Google Scholar]
  111. 111. 
    Furman JL, Holmes BB, Diamond MI 2015. Sensitive detection of proteopathic seeding activity with FRET flow cytometry. J. Vis. Exp. 106:e53205
    [Google Scholar]
  112. 112. 
    Kaufman SK, Thomas TL, Del Tredici K, Braak H, Diamond MI 2017. Characterization of tau prion seeding activity and strains from formaldehyde-fixed tissue. Acta Neuropathol. Commun. 5:41
    [Google Scholar]
  113. 113. 
    Kaufman SK, Sanders DW, Thomas TL, Ruchinskas AJ, Vaquer-Alicea J et al. 2016. Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo. Neuron 92:4796–812
    [Google Scholar]
  114. 114. 
    Furman JL, Vaquer-Alicea J, White CL, Cairns NJ, Nelson PT, Diamond MI 2017. Widespread tau seeding activity at early Braak stages. Acta Neuropathol 133:191–100
    [Google Scholar]
  115. 115. 
    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. 221:42231–49
    [Google Scholar]
  116. 116. 
    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 34:243028–41
    [Google Scholar]
  117. 117. 
    Katsinelos T, Zeitler M, Dimou E, Karakatsani A, Müller H-M et al. 2018. Unconventional secretion mediates the trans-cellular spreading of tau. Cell Rep 23:72039–55
    [Google Scholar]
  118. 118. 
    Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H et al. 1999. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:6740173–77
    [Google Scholar]
  119. 119. 
    Masliah E, Rockenstein E, Adame A, Alford M, Crews L et al. 2005. Effects of α-synuclein immunization in a mouse model of Parkinson's disease. Neuron 46:6857–68
    [Google Scholar]
  120. 120. 
    Tran HT, Chung CH-Y, Iba M, Zhang B, Trojanowski JQ et al. 2014. α-Synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep 7:62054–65
    [Google Scholar]
  121. 121. 
    Troquier L, Caillierez R, Burnouf S, J Fernandez-Gomez FJ, Grosjean M-E et al. 2012. Targeting phospho-Ser422 by active tau immunotherapy in the THYTau22 mouse model: a suitable therapeutic approach. Curr. Alzheimers Res. 9:4397–405
    [Google Scholar]
  122. 122. 
    Yanamandra K, Jiang H, Mahan TE, Maloney SE, Wozniak DF et al. 2015. Anti-tau antibody reduces insoluble tau and decreases brain atrophy. Ann. Clin. Transl. Neurol. 2:3278–88
    [Google Scholar]
  123. 123. 
    Congdon EE, Gu J, Sait HBR, Sigurdsson EM 2013. Antibody uptake into neurons occurs primarily via clathrin-dependent Fcγ receptor endocytosis and is a prerequisite for acute tau protein clearance. J. Biol. Chem. 288:4935452–65
    [Google Scholar]
  124. 124. 
    Gu J, Congdon EE, Sigurdsson EM 2013. Two novel Tau antibodies targeting the 396/404 region are primarily taken up by neurons and reduce Tau protein pathology. J. Biol. Chem. 288:4633081–95
    [Google Scholar]
  125. 125. 
    Rauch JN, Chen JJ, Sorum AW, Miller GM, Sharf T et al. 2018. Tau internalization is regulated by 6-O sulfation on heparan sulfate proteoglycans (HSPGs). Sci. Rep. 8:16382
    [Google Scholar]
  126. 126. 
    Oh SH, Kim HN, Park HJ, Shin JY, Bae E-J et al. 2016. Mesenchymal stem cells inhibit transmission of α-synuclein by modulating clathrin-mediated endocytosis in a Parkinsonian model. Cell Rep 14:4835–49
    [Google Scholar]
  127. 127. 
    Rubinsztein DC, Bento CF, Deretic V 2015. Therapeutic targeting of autophagy in neurodegenerative and infectious diseases. J. Exp. Med. 212:7979–90
    [Google Scholar]
  128. 128. 
    Sarkar S. 2013. Chemical screening platforms for autophagy drug discovery to identify therapeutic candidates for Huntington's disease and other neurodegenerative disorders. Drug Discov. Today Technol. 10:1e137–44
    [Google Scholar]
  129. 129. 
    Renna M, Jimenez-Sanchez M, Sarkar S, Rubinsztein DC 2010. Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J. Biol. Chem. 285:1511061–67
    [Google Scholar]
  130. 130. 
    Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M et al. 2008. Lithium delays progression of amyotrophic lateral sclerosis. PNAS 105:62052–57
    [Google Scholar]
  131. 131. 
    Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR et al. 2006. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 15:3433–42
    [Google Scholar]
  132. 132. 
    Aguib Y, Heiseke A, Gilch S, Riemer C, Baier M et al. 2009. Autophagy induction by trehalose counteracts cellular prion-infection. Autophagy 5:3361–69
    [Google Scholar]
  133. 133. 
    Heiseke A, Aguib Y, Riemer C, Baier M, Schätzl HM 2009. Lithium induces clearance of protease resistant prion protein in prion-infected cells by induction of autophagy. J. Neurochem. 109:125–34
    [Google Scholar]
  134. 134. 
    Miller TM, Pestronk A, David W, Rothstein J, Simpson E et al. 2013. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol 12:5435–42
    [Google Scholar]
  135. 135. 
    DeVos SL, Miller RL, Schoch KM, Holmes BB, Kebodeaux CS et al. 2017. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci. Transl. Med. 9:374eaag0481
    [Google Scholar]
  136. 136. 
    Doig AJ, Derreumaux P. 2015. Inhibition of protein aggregation and amyloid formation by small molecules. Curr. Opin. Struct. Biol. 30:50–56
    [Google Scholar]
  137. 137. 
    Aprile FA, Sormanni P, Perni M, Arosio P, Linse S et al. 2017. Selective targeting of primary and secondary nucleation pathways in Aβ42 aggregation using a rational antibody scanning method. Sci. Adv. 3:6e1700488
    [Google Scholar]
  138. 138. 
    Habchi J, Chia S, Limbocker R, Mannini B, Ahn M et al. 2017. Systematic development of small molecules to inhibit specific microscopic steps of Aβ42 aggregation in Alzheimer's disease. PNAS 114:2E200–8
    [Google Scholar]
  139. 139. 
    Shorter J. 2011. The mammalian disaggregase machinery: Hsp110 synergizes with Hsp70 and Hsp40 to catalyze protein disaggregation and reactivation in a cell-free system. PLOS ONE 6:10e26319
    [Google Scholar]
  140. 140. 
    Cohen SIA, Arosio P, Presto J, Kurudenkandy FR, Biverstal H et al. 2015. A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers. Nat. Struct. Mol. Biol. 22:3207–13
    [Google Scholar]
  141. 141. 
    Wickner RB. 2016. Yeast and fungal prions. Cold Spring Harb. Perspect. Biol. 8:9a023531
    [Google Scholar]
  142. 142. 
    Alberti S, Halfmann R, King O, Kapila A, Lindquist S 2009. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell 137:1146–58
    [Google Scholar]
  143. 143. 
    Halfmann R, Jarosz DF, Jones SK, Chang A, Lancaster AK, Lindquist S 2012. Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482:7385363–68
    [Google Scholar]
  144. 144. 
    True HL, Lindquist SL. 2000. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407:6803477–83
    [Google Scholar]
  145. 145. 
    True HL, Berlin I, Lindquist SL 2004. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431:7005184–87
    [Google Scholar]
  146. 146. 
    Nizhnikov AA, Antonets KS, Inge-Vechtomov SG, Derkatch IL 2014. Modulation of efficiency of translation termination in Saccharomyces cerevisiae. . Prion 8:3247–60
    [Google Scholar]
  147. 147. 
    Sweeny EA, Shorter J. 2016. Mechanistic and structural insights into the prion-disaggregase activity of Hsp104. J. Mol. Biol. 428:91870–85
    [Google Scholar]
  148. 148. 
    DeSantis ME, Leung EH, Sweeny EA, Jackrel ME, Cushman-Nick M et al. 2012. Operational plasticity enables Hsp104 to disaggregate diverse amyloid and nonamyloid clients. Cell 151:4778–93
    [Google Scholar]
  149. 149. 
    Tanaka M, Collins SR, Toyama BH, Weissman JS 2006. The physical basis of how prion conformations determine strain phenotypes. Nature 442:7102585–89
    [Google Scholar]
  150. 150. 
    Legname G, Nguyen H-OB, Peretz D, Cohen FE, DeArmond SJ, Prusiner SB 2006. Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. PNAS 103:5019105–10
    [Google Scholar]
  151. 151. 
    Collinge J, Clarke AR. 2007. A general model of prion strains and their pathogenicity. Science 318:5852930–36
    [Google Scholar]
  152. 152. 
    Dickinson AG, Meikle VMH. 1969. A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7. Genet. Res. 13:2213–25
    [Google Scholar]
  153. 153. 
    Stöhr J, Condello C, Watts JC, Bloch L, Oehler A et al. 2014. Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice. PNAS 111:2810329–34
    [Google Scholar]
  154. 154. 
    Watts JC, Condello C, Stöhr J, Oehler A, Lee J et al. 2014. Serial propagation of distinct strains of Aβ prions from Alzheimer's disease patients. PNAS 111:2810323–28
    [Google Scholar]
  155. 155. 
    Qiang W, Yau W-M, Lu J-X, Collinge J, Tycko R 2017. Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes. Nature 541:7636217–21
    [Google Scholar]
  156. 156. 
    Bousset L, Pieri L, Ruiz-Arlandis G, Gath J, Jensen PH et al. 2013. Structural and functional characterization of two alpha-synuclein strains. Nat. Commun. 4:2575
    [Google Scholar]
  157. 157. 
    Guo JL, Covell DJ, Daniels JP, Iba M, Stieber A et al. 2013. Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell 154:1103–17
    [Google Scholar]
  158. 158. 
    Boluda S, Iba M, Zhang B, Raible KM, Lee VM-Y, Trojanowski JQ 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 brains. Acta Neuropathol 129:2221–37
    [Google Scholar]
  159. 159. 
    Prusiner SB, Woerman AL, Mordes DA, Watts JC, Rampersaud R et al. 2015. Evidence for α-synuclein prions causing multiple system atrophy in humans with Parkinsonism. PNAS 112:38E5308–17
    [Google Scholar]
  160. 160. 
    Fitzpatrick A, Falcon B, He S, Murzin AG, Murshudov G et al. 2017. Cryo-EM structures of tau filaments from Alzheimer's disease. Nature 547:7662185–90
    [Google Scholar]
  161. 161. 
    Peelaerts W, Bousset L, Van der Perren A, Moskalyuk A, Pulizzi R et al. 2015. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522:7556340–44
    [Google Scholar]
  162. 162. 
    Woerman AL, Stöhr J, Aoyagi A, Rampersaud R, Krejciova Z et al. 2015. Propagation of prions causing synucleinopathies in cultured cells. PNAS 112:35E4949–58
    [Google Scholar]
  163. 163. 
    Woerman AL, Kazmi SA, Patel S, Aoyagi A, Oehler A et al. 2018. Familial Parkinson's point mutation abolishes multiple system atrophy prion replication. PNAS 115:2409–14
    [Google Scholar]
  164. 164. 
    Swinnen B, Robberecht W. 2014. The phenotypic variability of amyotrophic lateral sclerosis. Nat. Rev. Neurol. 10:11661–70
    [Google Scholar]
  165. 165. 
    Ravits J, Paul P, Jorg C 2007. Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology 68:191571–75
    [Google Scholar]
  166. 166. 
    Braak H, Braak E. 1991. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:4239–59
    [Google Scholar]
  167. 167. 
    Braak H, Braak E. 1995. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol. Aging 16:3271–78
    [Google Scholar]
  168. 168. 
    Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K 2006. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112:4389–404
    [Google Scholar]
  169. 169. 
    Agosta F, Weiler M, Filippi M 2015. Propagation of pathology through brain networks in neurodegenerative diseases: from molecules to clinical phenotypes. CNS Neurosci. Ther. 21:10754–67
    [Google Scholar]
  170. 170. 
    Greicius MD, Supekar K, Menon V, Dougherty RF 2009. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb. Cortex 19:172–78
    [Google Scholar]
  171. 171. 
    Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH et al. 2007. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 27:92349–56
    [Google Scholar]
  172. 172. 
    Vincent JL, Patel GH, Fox MD, Snyder AZ, Baker JT et al. 2007. Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447:714083–86
    [Google Scholar]
  173. 173. 
    Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD 2009. Neurodegenerative diseases target large-scale human brain networks. Neuron 62:142–52
    [Google Scholar]
  174. 174. 
    Zhou J, Gennatas ED, Kramer JH, Miller BL, Seeley WW 2012. Predicting regional neurodegeneration from the healthy brain functional connectome. Neuron 73:61216–27
    [Google Scholar]
  175. 175. 
    Raj A, Kuceyeski A, Weiner M 2012. A network diffusion model of disease progression in dementia. Neuron 73:61204–15
    [Google Scholar]
  176. 176. 
    Collinge J. 2016. Mammalian prions and their wider relevance in neurodegenerative diseases. Nature 539:7628217–26
    [Google Scholar]
  177. 177. 
    Cali I, Cohen ML, Haik S, Parchi P, Giaccone G et al. 2018. Iatrogenic Creutzfeldt-Jakob disease with amyloid-β pathology: an international study. Acta Neuropathol. Commun. 6:5
    [Google Scholar]
  178. 178. 
    Jaunmuktane Z, Quaegebeur A, Taipa R, Viana-Baptista M, Barbosa R et al. 2018. Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery. Acta Neuropathol 135:5671–79
    [Google Scholar]
  179. 179. 
    Marquié M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA et al. 2015. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann. Neurol. 78:5787–800
    [Google Scholar]
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