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Amyloid Accumulation and Pathogensis of Alzheimer’s Disease: Significance of Monomeric, Oligomeric and Fibrillar Aβ

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Book cover Alzheimer’s Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 38))

Abstract

This chapter reviews recent findings that indicate that soluble amyloid oligomers may represent the primary pathological species in Alzheimer’s and other degenerative diseases. Various amyloids share a number of common properties, including their structures and pathways for fibril formation and accumulation in disease. Recent findings suggest that toxic amyloid oligomers share a common structure, suggesting that they also share a common mechanism of pathogenesis

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References

  • Anguiano, M, Nowak R.J., and Lansbury, P.T. Jr, 2002, Protofibrillar islet amyloid polypeptide permeabilizes synthetic vesicles by a pore-like mechanism that may be relevant to type II diabetes. Biochemistry 41: 11338–11343.

    Article  PubMed  CAS  Google Scholar 

  • Antzutkin, O.N., Leapman, R.D., Balbach, J.J., and Tycko, R., 2002, Supramolecular structural constraints on Alzheimer’s beta-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance. Biochemistry 41:15436–15450.

    Article  PubMed  CAS  Google Scholar 

  • Balbach, J.J., Petkova, A.T., Oyler, N.A., Antzutkin, O.N., Gordon, D.J., Meredith, S.C., and Tycko, R., 2002, Supramolecular Structure in Full-Length Alzheimer’s beta-Amyloid Fibrils: Evidence for a Parallel beta-Sheet Organization from Solid-State Nuclear Magnetic Resonance. Biophys. J. 83: 1205–1216.

    PubMed  CAS  Google Scholar 

  • Bendiske, J., and Bahr, B.A., 2003, Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis—an approach for slowing Alzheimer disease?. J. Neuropathol. Exp. Neurol. 62: 451–463.

    PubMed  CAS  Google Scholar 

  • Benzinger, T.L., Gregory, D.M., Burkoth, T.S., Miller-Auer, H., Lynn, D.G., Botto, R.E., and Meredith, S.C., 1998, Propagating structure of Alzheimer’s beta-amyloid(10–35) is parallel beta-sheet with residues in exact register. Proc. Natl. Acad. Sci. USA 95: 13407–13412.

    Article  PubMed  CAS  Google Scholar 

  • Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C.M., and Stefani,. M., 2002, Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416: 507–511.

    Article  PubMed  CAS  Google Scholar 

  • Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., and Glabe. C., 1992, Assembly and aggregation properties of synthetic Alzheimer’s A4/beta amyloid peptide analogs. J. Biol. Chem. 267: 546–554.

    PubMed  CAS  Google Scholar 

  • Caughey, B., and Lansbury, P.T., 2003, Protoftbrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Ann. Rev. Neurosci. 26: 267–298.

    Article  PubMed  CAS  Google Scholar 

  • Dahlgren, K.N., Manelli, A.M., Stine, W.B Jr., Baker, L.K., Krafft, G.A., and LaDu, M.J.. 2002, Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J. Biol. Chem. 277: 32046–32053.

    Article  PubMed  CAS  Google Scholar 

  • Der-Sarkissian, A., Jao, C.C., Chen, J., and Langen, R., 2003, Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling. J Biol Chem. 278:37530–5.

    Article  PubMed  CAS  Google Scholar 

  • Dobson, C.M., 1999., Protein misfolding, evolution and disease. TIBS. 24: 3293–32.

    Google Scholar 

  • Esler, W.P., Stimson, E.R., Jennings, J.M., Vinters, H.V., Ghilardi, J.R., Lee, J.P., Mantyh, P.W., and Maggio, J.E., 2000, Alzheimer’s disease amyloid propagation by a template-dependent dock-lock mechanism. Biochemistry 39: 6288–6295.

    Article  PubMed  CAS  Google Scholar 

  • Fandrich, M., and Dobson, C.M., 2002, The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J. 21: 5682–5690.

    Article  PubMed  Google Scholar 

  • Garzon-Rodriguez, W., Sepulveda-Becerra, M., Milton, S., and Glabe, C.G., 1997, Soluble amyloid Abeta-(l–40) exists as a stable dimer at low concentrations. J Biol Chem. 272: 21037–21044.

    Article  PubMed  CAS  Google Scholar 

  • Garzon-Rodriguez, W., Vega, A., Sepulveda-Becerra, M., Milton, S., Johnson, D.A., Yatsimirsky, A.K., and Glabe, C.G., 2000, A conformation change in the carboxyl terminus of Alzheimer’s Abeta (1-40) accompanies the transition from dimer to fibril as revealed by fluorescence quenching analysis. J. Biol. Chem. 275: 22645–22649.

    Article  PubMed  CAS  Google Scholar 

  • Gong, Y., Chang, L., Viola, K.L, Lacor, P.N., Lambert, M.P., Finch, C.E., Krafft, G.A., and Klein, W.L., 2003, Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc. Natl. Acad. Sci. USA. 100: 10417–10422.

    Article  PubMed  CAS  Google Scholar 

  • Gregori, L., Fuchs, C, Figueiredo-Pereira, M.E., Van Nostrand, W.E., and Goldgaber, D., 1995, Amyloid beta-protein inhibits ubiquitin-dependent protein degradation in vitro. J. Biol. Chem. 270: 19702–19708.

    Article  PubMed  CAS  Google Scholar 

  • Hajimohammadreza, I., Anderson, V.E., Cavanagh, J.B., Seville, M.P., Nolan, C.C., Anderton, B.H., and Leigh, P.N., 1994, beta-Amyloid precursor protein fragments and lysosomal dense bodies are found in rat brain neurons after ventricular infusion of leupeptin. Brain Res. 640: 25–32.

    Article  PubMed  CAS  Google Scholar 

  • Hardy, J., and Selkoe. D.J., 2002, The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297: 353–356.

    Article  PubMed  CAS  Google Scholar 

  • Harper, J.D., Lieber, C.M., and Lansbury, P.T. 1997a, Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer’s disease amyloid-beta protein. Chem. Biol. 4: 951–959.

    Article  PubMed  CAS  Google Scholar 

  • Harper, J.D., Wong, S.S., Lieber, C.M., and Lansbury, P.T., 1997b, Observation of metastable Abeta amyloid protofibrils by atomic force microscopy. Chem Biol. 4: 119–125.

    Article  PubMed  CAS  Google Scholar 

  • Hartley, D.M., Walsh, D.M, Ye, C.P., Diehl, T., Vasquez, S., Vassilev, P.M., Teplow D.B., and Selkoe. D.J., 1999, Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19: 8876–8884.

    PubMed  CAS  Google Scholar 

  • Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C.L., and Beyreuther, K., 1991, Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer’s disease. J. Mol. Biol. 218: 149–163.

    Article  PubMed  CAS  Google Scholar 

  • Houlden, H., Baker, M., McGowan, E., Lewis, P., Hutton, M., Crook, R., Wood, N.W., Kumar-Singh, S., Geddes, J., Swash, M., Scaravilli, F., Holton, J.L., Lashley, T., Tomita, T., Hashimoto, T., Verkkoniemi, A., Kalimo, H., Somer, M., Paetau, A., Martin, J.J., Van Broeckhoven, C, Golde, T., Hardy, J., Haltia, M., and Revesz, T., 2000, Variant Alzheimer’s disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations. Ann. Neurol. 48: 806–808.

    Article  PubMed  CAS  Google Scholar 

  • Hsia, A.Y., Masliah, E., McConlogue, L., Yu, G.Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R.C., Nicoll, R.A., and Mucke, L., 1999, Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc. Natl. Acad. Sci. USA 96: 3228–3233.

    Article  PubMed  CAS  Google Scholar 

  • Kagan, B.L., Hirakura, Y., Azimov, R., Azimova, R., and Lin M.C., 2002, The channel hypothesis of Alzheimer’s disease: current status. Peptides. 23: 1311–1315.

    Article  PubMed  CAS  Google Scholar 

  • Kayed, R., Head, E., Thompson, J.L., McIntire, T.M., Milton, S.C., Cotman, C.W., and Glabe, C.G., 2003, Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300: 486–489.

    Article  PubMed  CAS  Google Scholar 

  • Keck, S., Nitsch, R., Grune, T., and Ullrich, O., 2003, Proteasome inhibition by paired helical filament-tau in brains of patients with Alzheimer’s disease. J. Neurochem. 85: 115–122.

    Article  PubMed  CAS  Google Scholar 

  • Kirkitadze, M.D., Bitan, G., and Teplow. D.B., 2002, Paradigm shifts in Alzheimer’s disease and other neurodegenerative disorders: the emerging role of oligomeric assemblies. J. Neurosci. Res. 69: 567–577.

    Article  PubMed  CAS  Google Scholar 

  • Klein, W.L., Krafft, G.A., and Finch, C.E., 2001, Targeting small Abeta oligomers: the solution to an Alzheimer’s disease conundrum? Trends Neurosci. 24: 219–224.

    Article  PubMed  CAS  Google Scholar 

  • Kuo, Y.M., Emmerling, M.R., Vigo-Pelfrey, C., Kasunic, T.C., Kirkpatrick, J.B., Murdoch, G.H., Ball, M.J., and Roher, A.E., 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 

  • Lashuel, H.A., Hartley, D., Petre, B.M., Walz, T., and Lansbury, P.T. Jr., 2002, Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418: 291.

    Article  PubMed  CAS  Google Scholar 

  • LeVine, H., 2002, 4,4(′)-Dianilino-l,l(′)-binaphthyl-5,5(′)-disulfonate: report on non-beta-sheet conformers of Alzheimer’s peptide beta (l–40). Arch. Biochem, Biophys. 404: 106–115.

    Article  CAS  Google Scholar 

  • LeVine, H.D., 1993, Thioflavinee T interaction with synthetic Alzheimer’s disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 2: 404–410.

    Article  PubMed  CAS  Google Scholar 

  • Lomakin, A., Teplow, D.B., Kirschner, D.A., and Benedek, G.B., 1997. Kinetic theory of fibrillogenesis of amyloid beta-protein. Proc. Natl. Acad. Sci. USA 94: 7942–7947.

    Article  PubMed  CAS  Google Scholar 

  • Lue, L.F., Kuo, Y.M., Roher, A.E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J.H., Rydel, R.E., and Rogers, J., 1999, Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Amer. J. Pathol. 155: 853–862.

    CAS  Google Scholar 

  • Mattson, M.P., 2002, Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer’s disease. J. Neurovirol. 8: 539–550.

    Article  PubMed  CAS  Google Scholar 

  • McLean, C.A., Cherny, R.A., Fraser, F.W., Fuller, S.J., Smith, M.J., Beyreuther, K., Bush, A.I., and Masters. C.L., 1999, Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann. Neural. 46: 860–866.

    Article  CAS  Google Scholar 

  • Petkova, A.T., Buntkowsky, G., Dyda, F., Leapman, R.D., Yau, W.M., and Tycko, R., 2004, Solid State NMR Reveals a pH-dependent Antiparallel beta-Sheet Registry in Fibrils Formed by a beta-Amyloid Peptide. J. Mol. Biol. 335: 247–260.

    Article  PubMed  CAS  Google Scholar 

  • Pitschke, M., Prior, R., Haupt, M., and Riesner, D., 1998, Detection of single amyloid beta-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy [see comments]. Nature Med. 4: 832–834.

    Article  PubMed  CAS  Google Scholar 

  • Shen, C.L., and Murphy, R.M., 1995, Solvent effects on self-assembly of beta-amyloid peptide. Biophys. J. 69: 640–651.

    PubMed  CAS  Google Scholar 

  • Soreghan, B., Kosmoski, J., and Glabe, C., 1994, Surfactant properties of Alzheimer’s A beta peptides and the mechanism of amyloid aggregation. J. Biol. Chem. 269: 28551–28554.

    PubMed  CAS  Google Scholar 

  • Terry, R.D., 1996, The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. J. Neuropathol Exp. Neurol. 55: 1023–1025.

    Article  PubMed  CAS  Google Scholar 

  • Torok, M., Milton, S., Kayed, R., Wu, P., McIntire, T., Glabe, C.C., and Langen, R., 2002, Structural and dynamic features of Alzheimer’s Abeta peptide in amyloid fibrils studied by site-directed spin labeling. J. Biol. Chem. 277: 40810–40815.

    Article  PubMed  CAS  Google Scholar 

  • Tseng, B.P., Esler, W.P., Clish, C.B., Stimson, E.R., Ghilardi, J.R., Vinters, H.V., Mantyh, P.W., Lee, J.P., and Maggio, J.E., 1999, Deposition of monomeric, not oligomeric, Abeta mediates growth of Alzheimer’s disease amyloid plaques in human brain preparations. Biochemistry 38: 10424–10431.

    Article  PubMed  CAS  Google Scholar 

  • Verkkoniemi, A., Somer, M., Rinne, J.O., Myllykangas, L., Crook, R., Hardy, J., Viitanen, M., Kalimo, H., and Haltia, M., 2000, Variant Alzheimer’s disease with spastic paraparesis: clinical characterization. Neurology 54: 1103–1109.

    PubMed  CAS  Google Scholar 

  • Waelter, S., Boeddrich, A., Lurz, R., Scherzinger, E., Lueder, G., Lehrach, H., and Wanker, E.E., 2001, Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 12: 1393–1407.

    PubMed  CAS  Google Scholar 

  • Walsh, D.M., Klyubin, I., Fadeeva, J.V., Rowan, M.J., and Selkoe, D.J., 2002, Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem. Soc. Trans. 30: 552–557.

    Article  PubMed  CAS  Google Scholar 

  • Walsh, D.M., Lomakin, A., Benedek, G.B., Condron, M.M., and Teplow, D.B., 1997, Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J. Biol. Chem. 272: 22364–22372.

    Article  PubMed  CAS  Google Scholar 

  • Westerman, M.A., Cooper-Blacketer, D., Mariash, A., Kotilinek, L., Kawarabayashi, T., Younkin, L.H., Carlson, G.A., Younkin, S.G., and Ashe, K.H., 2002, The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer’s disease. J. Neurosci. 22: 1858–1867.

    PubMed  CAS  Google Scholar 

  • Zagorski, M.G., Yang, J., Shao, H., Ma, K., Zeng, H., and Hong, A., 1999, Methodological and chemical factors affecting amyloid beta peptide amyloidogenicity. Meth. Enzymol. 309: 189–204.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. University of California, Irvine, Irvine, CA, 92697, USA

    Charles C. Glabe

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  1. Charles C. Glabe
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  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Institute of Biochemistry, University of Mainz, Mainz, Germany

    Falk Fahrenholz

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Glabe, C.C. (2005). Amyloid Accumulation and Pathogensis of Alzheimer’s Disease: Significance of Monomeric, Oligomeric and Fibrillar Aβ. In: Harris, J.R., Fahrenholz, F. (eds) Alzheimer’s Disease. Subcellular Biochemistry, vol 38. Springer, Boston, MA . https://doi.org/10.1007/0-387-23226-5_8

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