Diffusible, highly bioactive oligomers represent a critical minority of soluble Aβ in Alzheimer’s disease brain (original) (raw)

References

  1. Barry AE, Klyubin I, Mc Donald JM, Mably AJ, Farrell MA, Scott M, Walsh DM, Rowan MJ (2011) Alzheimer’s disease brain-derived amyloid-beta-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J Neurosci 31:7259–7263
    Article PubMed CAS Google Scholar
  2. Benilova I, Karran E, De Strooper B (2012) The toxic Abeta oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci 15:349–357
    Article PubMed CAS Google Scholar
  3. Borlikova GG, Trejo M, Mably AJ, Mc Donald JM, Sala Frigerio C, Regan CM, Murphy KJ, Masliah E, Walsh DM (2013) Alzheimer brain-derived amyloid beta-protein impairs synaptic remodeling and memory consolidation. Neurobiol Aging 34:1315–1327
    Article PubMed CAS Google Scholar
  4. Brody DL, Jiang H, Wildburger N, Esparza TJ (2017) Non-canonical soluble amyloid-beta aggregates and plaque buffering: controversies and future directions for target discovery in Alzheimer’s disease. Alzheimers Res Ther 9:62
    Article PubMed PubMed Central CAS Google Scholar
  5. De Felice FG, Wu D, Lambert MP, Fernandez SJ, Velasco PT, Lacor PN, Bigio EH, Jerecic J, Acton PJ, Shughrue PJ, Chen-Dodson E, Kinney GG, Klein WL (2008) Alzheimer’s disease-type neuronal tau hyperphosphorylation induced by A beta oligomers. Neurobiol Aging 29:1334–1347
    Article PubMed CAS Google Scholar
  6. Enya M, Morishima-Kawashima M, Yoshimura M, Shinkai Y, Kusui K, Khan K, Games D, Schenk D, Sugihara S, Yamaguchi H, Ihara Y (1999) Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in the cortex during aging. Am J Pathol 154:271–279
    Article PubMed PubMed Central CAS Google Scholar
  7. Esparza TJ, Wildburger NC, Jiang H, Gangolli M, Cairns NJ, Bateman RJ, Brody DL (2016) Soluble amyloid-beta aggregates from human Alzheimer’s disease brains. Sci Rep 6:38187
    Article PubMed PubMed Central CAS Google Scholar
  8. Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, Brody DL (2013) Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol 73:104–119
    Article PubMed CAS Google Scholar
  9. Freir DB, Nicoll AJ, Klyubin I, Panico S, Mc Donald JM, Risse E, Asante EA, Farrow MA, Sessions RB, Saibil HR, Clarke AR, Rowan MJ, Walsh DM, Collinge J (2011) Interaction between prion protein and toxic amyloid beta assemblies can be therapeutically targeted at multiple sites. Nat Commun 2:336
    Article PubMed PubMed Central CAS Google Scholar
  10. Funato H, Enya M, Yoshimura M, Morishima-Kawashima M, Ihara Y (1999) Presence of sodium dodecyl sulfate-stable amyloid beta-protein dimers in the hippocampus CA1 not exhibiting neurofibrillary tangle formation. Am J Pathol 155:23–28
    Article PubMed PubMed Central CAS Google Scholar
  11. Glabe CG (2008) Structural classification of toxic amyloid oligomers. J Biol Chem 283:29639–29643
    Article PubMed PubMed Central CAS Google Scholar
  12. Golde TE (2014) Open questions for Alzheimer’s disease immunotherapy. Alzheimers Res Ther 6:3
    Article PubMed PubMed Central Google Scholar
  13. Golde TE, Schneider LS, Koo EH (2011) Anti-abeta therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron 69:203–213
    Article PubMed PubMed Central CAS Google Scholar
  14. Jack CR Jr, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, Zeng G, Bernstein MA, Gunter JL, Pankratz VS, Aisen PS, Weiner MW, Petersen RC, Shaw LM, Trojanowski JQ, Knopman DS, ADNI (2010) Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease. Brain 133:3336–3348
    Article PubMed PubMed Central Google Scholar
  15. Jan A, Adolfsson O, Allaman I, Buccarello AL, Magistretti PJ, Pfeifer A, Muhs A, Lashuel HA (2011) Abeta42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete Abeta42 species. J Biol Chem 286:8585–8596
    Article PubMed CAS Google Scholar
  16. Jin M, O’Nuallain B, Hong W, Boyd JD, Lagomarsino VN, O’Malley TT, Liu W, Vanderburg CR, Frosch MP, Young-Pearse TL, Selkoe DJ, Walsh DM (2018) A new paradigm to assess the therapeutic potential of anti-Aβ antibodies for Alzheimer’s disease. (submitted)
  17. Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ (2011) Soluble amyloid beta-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci USA 108:5819–5824
    Article PubMed Google Scholar
  18. Johnson-Wood K, Lee M, Motter R, Hu K, Gordon G, Barbour R, Khan K, Gordon M, Tan H, Games D, Lieberburg I, Schenk D, Seubert P, McConlogue L (1997) Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci USA 94:1550–1555
    Article PubMed CAS Google Scholar
  19. Jones KR, Reichardt LF (1990) Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci USA 87:8060–8064
    Article PubMed CAS Google Scholar
  20. Kim J, Eltorai AE, Jiang H, Liao F, Verghese PB, Kim J, Stewart FR, Basak JM, Holtzman DM (2012) Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Abeta amyloidosis. J Exp Med 209:2149–2156
    Article PubMed PubMed Central CAS Google Scholar
  21. Klyubin I, Cullen WK, Hu NW, Rowan MJ (2012) Alzheimer’s disease Abeta assemblies mediating rapid disruption of synaptic plasticity and memory. Mol Brain 5:25
    Article PubMed PubMed Central CAS Google Scholar
  22. Klyubin I, Walsh DM, Lemere CA, Cullen WK, Shankar GM, Betts V, Spooner ET, Jiang L, Anwyl R, Selkoe DJ, Rowan MJ (2005) Amyloid beta protein immunotherapy neutralizes Abeta oligomers that disrupt synaptic plasticity in vivo. Nat Med 11:556–561
    Article PubMed CAS Google Scholar
  23. Kuo YM, Emmerling MR, Vigo-Pelfrey C, Kasunic TC, Kirkpatrick JB, Murdoch GH, Ball MJ, Roher AE (1996) Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J Biol Chem 271:4077–4081
    Article PubMed CAS Google Scholar
  24. Lannfelt L, Moller C, Basun H, Osswald G, Sehlin D, Satlin A, Logovinsky V, Gellerfors P (2014) Perspectives on future Alzheimer therapies: amyloid-beta protofibrils—a new target for immunotherapy with BAN2401 in Alzheimer’s disease. Alzheimers Res Ther 6:16
    Article PubMed PubMed Central Google Scholar
  25. Lasagna-Reeves CA, Glabe CG, Kayed R (2011) Amyloid-beta annular protofibrils evade fibrillar fate in Alzheimer disease brain. J Biol Chem 286:22122–22130
    Article PubMed PubMed Central CAS Google Scholar
  26. Liu P, Reed MN, Kotilinek LA, Grant MK, Forster CL, Qiang W, Shapiro SL, Reichl JH, Chiang AC, Jankowsky JL, Wilmot CM, Cleary JP, Zahs KR, Ashe KH (2015) Quaternary structure defines a large class of amyloid-beta oligomers neutralized by sequestration. Cell Rep 11:1760–1771
    Article PubMed PubMed Central CAS Google Scholar
  27. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol 155:853–862
    Article PubMed PubMed Central CAS Google Scholar
  28. Mably AJ, Liu W, Mc Donald JM, Dodart JC, Bard F, Lemere CA, O’Nuallain B, Walsh DM (2015) Anti-Abeta antibodies incapable of reducing cerebral Abeta oligomers fail to attenuate spatial reference memory deficits in J20 mice. Neurobiol Dis 82:372–384
    Article PubMed PubMed Central CAS Google Scholar
  29. Mc Donald JM, O’Malley TT, Liu W, Mably AJ, Brinkmalm G, Portelius E, Wittbold WM 3rd, Frosch MP, Walsh DM (2015) The aqueous phase of Alzheimer’s disease brain contains assemblies built from approximately 4 and approximately 7 kDa Abeta species. Alzheimers Dement 11:1286–1305
    Article PubMed PubMed Central Google Scholar
  30. Mc Donald JM, Savva GM, Brayne C, Welzel AT, Forster G, Shankar GM, Selkoe DJ, Ince PG, Walsh DM (2010) The presence of sodium dodecyl sulphate-stable Abeta dimers is strongly associated with Alzheimer-type dementia. Brain 133:1328–1341
    Article PubMed PubMed Central Google Scholar
  31. McDonald JM, Cairns NJ, Taylor-Reinwald L, Holtzman D, Walsh DM (2012) The levels of water-soluble and triton-soluble Abeta are increased in Alzheimer’s disease brain. Brain Res 1450:138–147
    Article PubMed CAS Google Scholar
  32. McLaurin J, Cecal R, Kierstead ME, Tian X, Phinney AL, Manea M, French JE, Lambermon MH, Darabie AA, Brown ME, Janus C, Chishti MA, Horne P, Westaway D, Fraser PE, Mount HT, Przybylski M, St George-Hyslop P (2002) Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4–10 and inhibit cytotoxicity and fibrillogenesis. Nat Med 8:1263–1269
    Article PubMed CAS Google Scholar
  33. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 46:860–866
    Article PubMed CAS Google Scholar
  34. Noguchi A, Matsumura S, Dezawa M, Tada M, Yanazawa M, Ito A, Akioka M, Kikuchi S, Sato M, Ideno S, Noda M, Fukunari A, Muramatsu S, Itokazu Y, Sato K, Takahashi H, Teplow DB, Nabeshima Y, Kakita A, Imahori K, Hoshi M (2009) Isolation and characterization of patient-derived, toxic, high mass amyloid beta-protein (Abeta) assembly from Alzheimer disease brains. J Biol Chem 284:32895–32905
    Article PubMed PubMed Central CAS Google Scholar
  35. Palmert MR, Podlisny MB, Witker DS, Oltersdorf T, Younkin LH, Selkoe DJ, Younkin SG (1989) The beta-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc Natl Acad Sci USA 86:6338–6342
    Article PubMed CAS Google Scholar
  36. Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE, Teplow DB, Selkoe DJ (1995) Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable oligomers in cell culture. J Biol Chem 270:9564–9570
    Article PubMed CAS Google Scholar
  37. Roher AE, Chaney MO, Kuo YM, Webster SD, Stine WB, Haverkamp LJ, Woods AS, Cotter RJ, Tuohy JM, Krafft GA, Bonnell BS, Emmerling MR (1996) Morphology and toxicity of Abeta-(1-42) dimer derived from neuritic and vascular amyloid deposits of Alzheimer’s disease. J Biol Chem 271:20631–20635
    Article PubMed CAS Google Scholar
  38. Sala Frigerio C, Fadeeva JV, Minogue AM, Citron M, Van Leuven F, Staufenbiel M, Paganetti P, Selkoe DJ, Walsh DM (2010) beta-Secretase cleavage is not required for generation of the intracellular C-terminal domain of the amyloid precursor family of proteins. FEBS J 277:1503–1518
    Article PubMed CAS Google Scholar
  39. Sehlin D, Englund H, Simu B, Karlsson M, Ingelsson M, Nikolajeff F, Lannfelt L, Pettersson FE (2012) Large aggregates are the major soluble Abeta species in AD brain fractionated with density gradient ultracentrifugation. PLoS ONE 7:e32014
    Article PubMed PubMed Central CAS Google Scholar
  40. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608
    Article PubMed PubMed Central CAS Google Scholar
  41. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C et al (1992) Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature 359:325–327
    Article PubMed CAS Google Scholar
  42. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14:837–842
    Article PubMed PubMed Central CAS Google Scholar
  43. Shankar GM, Walsh DM (2009) Alzheimer’s disease: synaptic dysfunction and Abeta. Mol Neurodegener 4:48
    Article PubMed PubMed Central CAS Google Scholar
  44. Shankar GM, Welzel AT, McDonald JM, Selkoe DJ, Walsh DM (2011) Isolation of low-n amyloid beta-protein oligomers from cultured cells, CSF, and brain. Methods Mol Biol 670:33–44
    Article PubMed CAS Google Scholar
  45. Simpson J, Bladon CM, Yates CM, Harmar AJ (1988) An antiserum to the C-terminus of the Alzheimer amyloid precursor recognizes a soluble 70 kDa protein. FEBS Lett 237:196–198
    Article PubMed CAS Google Scholar
  46. Sui L, Wang Y, Ju LH, Chen M (2012) Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex. Neurobiol Learn Mem 97:425–440
    Article PubMed CAS Google Scholar
  47. Szczepankiewicz O, Linse B, Meisl G, Thulin E, Frohm B, Sala Frigerio C, Colvin MT, Jacavone AC, Griffin RG, Knowles T, Walsh DM, Linse S (2015) N-terminal extensions retard Abeta42 fibril formation but allow cross-seeding and coaggregation with Abeta42. J Am Chem Soc 137:14673–14685
    Article PubMed PubMed Central CAS Google Scholar
  48. Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, Strittmatter SM (2012) Alzheimer amyloid-beta oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci 15:1227–1235
    Article PubMed PubMed Central CAS Google Scholar
  49. Upadhaya AR, Lungrin I, Yamaguchi H, Fandrich M, Thal DR (2012) High-molecular weight Abeta oligomers and protofibrils are the predominant Abeta species in the native soluble protein fraction of the AD brain. J Cell Mol Med 16:287–295
    Article PubMed PubMed Central CAS Google Scholar
  50. Viola KL, Klein WL (2015) Amyloid beta oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis. Acta Neuropathol 129:183–206
    Article PubMed PubMed Central CAS Google Scholar
  51. Walsh DM, Selkoe DJ (2004) Deciphering the molecular basis of memory failure in Alzheimer’s disease. Neuron 44:181–193
    Article PubMed CAS Google Scholar
  52. Walsh DM, Teplow DB (2012) Alzheimer’s disease and the amyloid beta-protein. Prog Mol Biol Transl Sci 107:101–124
    Article PubMed CAS Google Scholar
  53. Wang J, Dickson DW, Trojanowski JQ, Lee VM (1999) The levels of soluble versus insoluble brain Abeta distinguish Alzheimer’s disease from normal and pathologic aging. Exp Neurol 158:328–337
    Article PubMed CAS Google Scholar
  54. Wang Z, Jackson RJ, Hong W, Taylor WM, Corbett GT, Moreno A, Liu W, Li S, Frosch MP, Slutsky I, Young-Pearse TL, Spires-Jones TL, Walsh DM (2017) Human brain-derived abeta oligomers bind to synapses and disrupt synaptic activity in a manner that requires APP. J Neurosci 37:11947–11966
    Article PubMed PubMed Central CAS Google Scholar
  55. Watson D, Castano E, Kokjohn TA, Kuo YM, Lyubchenko Y, Pinsky D, Connolly ES Jr, Esh C, Luehrs DC, Stine WB, Rowse LM, Emmerling MR, Roher AE (2005) Physicochemical characteristics of soluble oligomeric Abeta and their pathologic role in Alzheimer’s disease. Neurol Res 27:869–881
    Article PubMed CAS Google Scholar
  56. Welzel AT, Maggio JE, Shankar GM, Walker DE, Ostaszewski BL, Li S, Klyubin I, Rowan MJ, Seubert P, Walsh DM, Selkoe DJ (2014) Secreted amyloid beta-proteins in a cell culture model include N-terminally extended peptides that impair synaptic plasticity. Biochemistry 53:3908–3921
    Article PubMed PubMed Central CAS Google Scholar
  57. Willem M, Tahirovic S, Busche MA, Ovsepian SV, Chafai M, Kootar S, Hornburg D, Evans LD, Moore S, Daria A, Hampel H, Muller V, Giudici C, Nuscher B, Wenninger-Weinzierl A, Kremmer E, Heneka MT, Thal DR, Giedraitis V, Lannfelt L, Muller U, Livesey FJ, Meissner F, Herms J, Konnerth A, Marie H, Haass C (2015) eta-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 526:443–447
    Article PubMed CAS Google Scholar
  58. Wogulis M, Wright S, Cunningham D, Chilcote T, Powell K, Rydel RE (2005) Nucleation-dependent polymerization is an essential component of amyloid-mediated neuronal cell death. J Neurosci 25:1071–1080
    Article PubMed CAS Google Scholar
  59. Yang T, Li S, Xu H, Walsh DM, Selkoe DJ (2017) Large soluble oligomers of amyloid beta-protein from Alzheimer brain are far less neuroactive than the smaller oligomers to which they dissociate. J Neurosci 37:152–163
    Article PubMed PubMed Central CAS Google Scholar
  60. Yang T, O’Malley TT, Kanmert D, Jerecic J, Zieske LR, Zetterberg H, Hyman BT, Walsh DM, Selkoe DJ (2015) A highly sensitive novel immunoassay specifically detects low levels of soluble Abeta oligomers in human cerebrospinal fluid. Alzheimers Res Ther 7:14
    Article PubMed PubMed Central CAS Google Scholar
  61. Yankner BA, Lu T (2009) Amyloid beta-protein toxicity and the pathogenesis of Alzheimer disease. J Biol Chem 284:4755–4759
    Article PubMed PubMed Central CAS Google Scholar
  62. Zeng H, Guo M, Martins-Taylor K, Wang X, Zhang Z, Park JW, Zhan S, Kronenberg MS, Lichtler A, Liu HX, Chen FP, Yue L, Li XJ, Xu RH (2010) Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells. PLoS ONE 5:e11853
    Article PubMed PubMed Central CAS Google Scholar
  63. Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W, Yang N, Danko T, Chen L, Wernig M, Sudhof TC (2013) Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78:785–798
    Article PubMed PubMed Central CAS Google Scholar

Download references