Alzheimer's disease: synaptic dysfunction and Abeta

Ganesh M Shankar, Dominic M Walsh, Ganesh M Shankar, Dominic M Walsh

Abstract

Synapse loss is an early and invariant feature of Alzheimer's disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid beta-protein (Abeta) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Abeta are mediators of synaptic compromise. We also discuss the possible mechanisms of Abeta synaptotoxicity and potential targets for therapeutic intervention.

References

    1. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–2117.
    1. Kawas CH. Clinical practice. Early Alzheimer'sdisease. N Engl J Med. 2003;349:1056–1063.
    1. Nussbaum RL, Ellis CE. Alzheimer's disease and Parkinson's disease. N Engl J Med. 2003;348:1356–1364.
    1. Mercy L, Hodges JR, Dawson K, Barker RA, Brayne C. Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology. 2008;71:1496–1499.
    1. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001;81:741–766.
    1. Romanelli MF, Morris JC, Ashkin K, Coben LA. Advanced Alzheimer's disease is a risk factor for late-onset seizures. Arch Neurol. 1990;47:847–850.
    1. Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol. 1985;42:1097–1105.
    1. Gomez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997;41:17–24.
    1. Uylings HB, de Brabander JM. Neuronal changes in normal human aging and Alzheimer's disease. Brain Cogn. 2002;49:268–276.
    1. Alzheimer A. Über einen eigenartigen schweren Erkrankungsprozeβ der Hirnrinde. Neurologisches Centralblatt. 1906;23:1129–1136.
    1. Terry RD. The fine structure of neurofibrillary tangles in Alzheimer's disease. J Neuropathol Exp Neurol. 1963;22:629–642.
    1. Kidd M. Alzheimer's disease - An electron microscopical study. Brain. 1964;87:307–320.
    1. Davies CA, Mann DM, Sumpter PQ, Yates PO. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J Neurol Sci. 1987;78:151–164.
    1. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr, Morris JC. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology. 2001;56:127–129.
    1. Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology. 2007;68:1501–1508.
    1. Cajal Ry. Degeneration and regeneration of the nervous system. Oxford Press, London; 1928.
    1. Bertoni-Freddari C, Fattoretti P, Meier-Ruge W, Ulrich J. Computer-assisted morphometry of synaptic plasticity during aging and dementia. Pathol Res Pract. 1989;185:799–802.
    1. DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol. 1990;27:457–464.
    1. Masliah E, Cole G, Shimohama S, Hansen L, DeTeresa R, Terry RD, Saitoh T. Differential involvement of protein kinase C isozymes in Alzheimer's disease. J Neurosci. 1990;10:2113–2124.
    1. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572–580.
    1. Sze CI, Troncoso JC, Kawas C, Mouton P, Price DL, Martin LJ. Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol. 1997;56:933–944.
    1. Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, Kaye J, Manczak M. Differential loss of synaptic proteins in Alzheimer's disease: implications for synaptic dysfunction. J Alzheimers Dis. 2005;7:103–117. discussion 173-180.
    1. Bertoni-Freddari C, Fattoretti P, Casoli T, Caselli U, Meier-Ruge W. Deterioration threshold of synaptic morphology in aging and senile dementia of Alzheimer's type. Anal Quant Cytol Histol. 1996;18:209–213.
    1. Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–1384.
    1. Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry. 1957;20:11–21.
    1. Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci. 1986;6:2950–2967.
    1. deToledo-Morrell L, Geinisman Y, Morrell F. Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders. Neurobiol Aging. 1988;9:581–590.
    1. Geinisman Y, de Toledo-Morrell L, Morrell F. Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats. Proc Natl Acad Sci USA. 1986;83:3027–3031.
    1. Geinisman Y, de Toledo-Morrell L, Morrell F. Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory. Brain Res. 1986;398:266–275.
    1. Geinisman Y, deToledo-Morrell L, Morrell F, Persina IS, Rossi M. Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique. Hippocampus. 1992;2:437–444.
    1. Barnes CA. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979;93:74–104.
    1. Hyman BT, Van Hoesen GW, Kromer LJ, Damasio AR. Perforant pathway changes and the memory impairment of Alzheimer's disease. Ann Neurol. 1986. pp. 472–481.
    1. Geinisman Y. Age-related decline in memory function: is it associated with a loss of synapses? Neurobiol Aging. 1999;20:353–356. discussion 359-360.
    1. Morris RG. Long-term potentiation and memory. Philos Trans R Soc Lond B Biol Sci. 2003;358:643–647.
    1. Lynch MA. Long-term potentiation and memory. Physiol Rev. 2004;84:87–136.
    1. Buckner RL. Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron. 2004;44:195–208.
    1. Persson J, Nyberg L, Lind J, Larsson A, Nilsson LG, Ingvar M, Buckner RL. Structure-function correlates of cognitive decline in aging. Cereb Cortex. 2006;16:907–915.
    1. Mesulam MM. Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles. Neuron. 1999;24:521–529.
    1. Hebb DO. A Neuropsychological Theory. Lawrence Erlbaum Associates, Mahwah N, J; 1949.
    1. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron. 2004;44:5–21.
    1. Whitlock JR, Heynen AJ, Shuler MG, Bear MF. Learning induces long-term potentiation in the hippocampus. Science. 2006;313:1093–1097.
    1. Kemp N, Bashir ZI. Long-term depression: a cascade of induction and expression mechanisms. Prog Neurobiol. 2001;65:339–365.
    1. Citri A, Malenka RC. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008;33:18–41.
    1. Colbran RJ. Targeting of calcium/calmodulin-dependent protein kinase II. Biochem J. 2004;378:1–16.
    1. Kessels HW, Kopec CD, Klein ME, Malinow R. Roles of stargazin and phosphorylation in the control of AMPA receptor subcellular distribution. Nat Neurosci. 2009;12:888–896.
    1. Kessels HW, Malinow R. Synaptic AMPA receptor plasticity and behavior. Neuron. 2009;61:340–350.
    1. Matsuzaki M, Honkura N, Ellis-Davies GC, Kasai H. Structural basis of long-term potentiation in single dendritic spines. Nature. 2004;429:761–766.
    1. Zhou Q, Homma KJ, Poo MM. Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron. 2004;44:749–757.
    1. Bastrikova N, Gardner GA, Reece JM, Jeromin A, Dudek SM. Synapse elimination accompanies functional plasticity in hippocampal neurons. Proc Natl Acad Sci USA. 2008;105:3123–3127.
    1. Lamprecht R, LeDoux J. Structural plasticityand memory. Nat Rev Neurosci. 2004;5:45–54.
    1. Holtmaat A, Wilbrecht L, Knott GW, Welker E, Svoboda K. Experience-dependent and cell-type-specific spine growth in the neocortex. Nature. 2006;441:979–983.
    1. Klein WL, Krafft GA, Finch CE. Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum? Trends Neurosci. 2001;24:219–224.
    1. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298:789–791.
    1. Walsh DM, Selkoe DJ. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron. 2004;44:181–193.
    1. Selkoe DJ. Clearing the brain's amyloid cobwebs. Neuron. 2001;32:177–180.
    1. Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron. 2005;48:913–922.
    1. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–356.
    1. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009;78:959–991.
    1. Walsh DM, Selkoe DJ. A beta oligomers - a decade of discovery. J Neurochem. 2007;101:1172–1184.
    1. Katzman R. Alzheimer's disease. N Engl J Med. 1986;314:964–973.
    1. Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging. 1995;16:285–298. discussion 298-304.
    1. Harper JD, Wong SS, Lieber CM, Lansbury PT Jr. Observation of metastable Aβ amyloid protofibrils by atomic force microscopy. Chem & Biol. 1997;4:119–125.
    1. Walsh DM, Hartley DM, Kusumoto Y, Fezoui Y, Condron MM, Lomakin A, Benedek GB, Selkoe DJ, Teplow DB. Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J Biol Chem. 1999;274:25945–25952.
    1. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, iosatos M, Morgan TE, Rozovsky I, Trommer B, Viola KL, Wals P, Zhang C, Finch CE, Krafft GA, Klein WL. Diffusible, nonfribrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci USA. 1998;95:6448–6453.
    1. Hoshi M, Sato M, Matsumoto S, Noguchi A, Yasutake K, Yoshida N, Sato K. Spherical aggregates of beta-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3beta. Proc Natl Acad Sci USA. 2003;100:6370–6375.
    1. Bitan G, Kirkitadze MD, Lomakin A, Vollers SS, Benedek GB, Teplow DB. Amyloid β-protein (Aβ) assembly: Aβ 40 and Aβ 42 oligomerize through distinct pathways. Proc Natl Acad Sci USA. 2003;100:330–335.
    1. Lemere CA, Spooner ET, Leverone JF, Mori C, Clements JD. Intranasal immunotherapy for the treatment of Alzheimer's disease: Escherichia coli LT and LT(R192G) as mucosal adjuvants. Neurobiol Aging. 2002;23:991–1000.
    1. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, Bush AI, Masters CL. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol. 1999;46:860–866.
    1. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L, Beach T, Kurth JH, Rydel RE, Rogers J. Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am J Pathol. 1999;155:853–862.
    1. Wang J, Dickson DW, Trojanowski JQ, Lee VM. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging. Exp Neurol. 1999;158:328–337.
    1. Kuo YM, Emmerling MR, Vigo-Pelfrey C, Kasunic TC, Kirkpatrick JB, Murdoch GH, Ball MJ, Roher AE. Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J Biol Chem. 1996;271:4077–4081.
    1. Stenh C, Englund H, Lord A, Johansson AS, Almeida CG, Gellerfors P, Greengard P, Gouras GK, Lannfelt L, Nilsson LN. Amyloid-beta oligomers are inefficiently measured by enzyme-linked immunosorbent assay. Ann Neurol. 2005;58:147–150.
    1. Morishima-Kawashima M, Ihara Y. The presence of amyloid β-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells. Biochem. 1998;37:15247–15253.
    1. Enya M, Morishima-Kawashima M, Yoshimura M, Shinkai Y, Kusui K, Khan K, Games D, Schenk D, Sugihara S, Yamaguchi H, Ihara Y. Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in the cortex during aging. Am J Pathol. 1999;154:271–279.
    1. Funato H, Enya M, Yoshimura M, Morishima-Kawashima M, Ihara Y. Presence of sodium dodecyl sulfate-stable amyloid beta-protein dimers in the hippocampus CA1 not exhibiting neurofibrillary tangle formation. Am J Pathol. 1999;155:23–28.
    1. Englund H, Degerman Gunnarsson M, Brundin RM, Hedlund M, Kilander L, Lannfelt L, Ekholm Pettersson F. Oligomerization Partially Explains the Lowering of Abeta42 in Alzheimer's Disease Cerebrospinal Fluid. Neurodegener Dis. 2009;6:139–147.
    1. 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. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008;14:837–842.
    1. Vigo-Pelfrey C, Lee D, Keim PS, Lieberburg I, Schenk D. Characterization of beta-amyloid peptide from human cerebrospinal fluid. Journal Neurochemistry. 1993;61:1965–1968.
    1. Roher A, Wolfe D, Palutke M, KuKuruga D. Purification, ultrastructure, and chemical analyses of Alzheimer's disease amyloid plaque core protein. Proc Natl Acad Sci USA. 1986;83:2662–2666.
    1. Ashe KH. Learning and memory in transgenic mice modeling Alzheimer's disease. Learn Mem. 2001;8:301–308.
    1. Games D, Buttini M, Kobayashi D, Schenk D, Seubert P. Mice as models: transgenic approaches and Alzheimer's disease. J Alzheimers Dis. 2006;9:133–149.
    1. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, Hu K, Kholodenko D, Johnson-Wood K, McConlogue L. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci. 2000;20:4050–4058.
    1. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA. 1999;96:3228–3233.
    1. Westerman MA, Cooper-Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin LH, Carlson GA, Younkin SG, Ashe KH. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2002;22:1858–1867.
    1. Kawarabayashi T, Shoji M, Younkin LH, Wen-Lang L, Dickson DW, Murakami T, Matsubara E, Abe K, Ashe KH, Younkin SG. Dimeric amyloid beta protein rapidly accumulates in lipid rafts followed by apolipoprotein E and phosphorylated tau accumulation in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2004;24:3801–3809.
    1. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006;440:352–357.
    1. Cheng IH, Scearce-Levie K, Legleiter J, Palop JJ, Gerstein H, Bien-Ly N, Puolivali J, Lesne S, Ashe KH, Muchowski PJ, Mucke L. Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem. 2007;282:23818–23828.
    1. Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM, Paul SM. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci. 2002;5:452–457.
    1. Reed MN, Hofmeister JJ, Jungbauer L, Welzel AT, Yu C, Lesné S, LaDu MJ, Walsh DM, Ashe KH, Cleary JP. Cognitive Effects of Naturally and Synthetically Derived A® Oligomers. Neurobiology of Aging. 2009. in press .
    1. Dineley KT, Xia XF, Bui D, Sweatt JD, Zheng H. Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins. Journal of Biological Chemistry. 2002;277:22768–22780.
    1. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA. 2006;103:5161–5166.
    1. Shankar GM, Leissring MA, Adame A, Sun X, Spooner E, Masliah E, Selkoe DJ, Lemere CA, Walsh DM. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol Dis. 2009;36:293–302.
    1. Meilandt WJ, Cisse M, Ho K, Wu T, Esposito LA, Scearce-Levie K, Cheng IH, Yu GQ, Mucke L. Neprilysin overexpression inhibits plaque formation but fails to reduce pathogenic Abeta oligomers and associated cognitive deficits in human amyloid precursor protein transgenic mice. J Neurosci. 2009;29:1977–1986.
    1. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009;62:788–801.
    1. Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE, Teplow DB, Selkoe DJ. Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable oligomers in cell culture. J Biol Chem. 1995;270:9564–9570.
    1. Xia W, Zhang J, Kholodenko D, Citron M, Podlisny MB, Teplow DB, Haass C, Seubert P, Koo EH, Selkoe DJ. Enhanced production and oligomerization of the 42-residue amyloid beta-protein by Chinese hamster ovary cells stably expressing mutant presenilins. Journal Biological Chemistry. 1997;272:7977–7982.
    1. Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ. The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry. 2000;39:10831–10839.
    1. Townsend M, Shankar GM, Mehta T, Walsh DM, Selkoe DJ. Effects of secreted oligomers of amyloid {beta}-protein on hippocampal synaptic plasticity: a potent role for trimers. J Physiol. 2006;572:477–492.
    1. Poling A, Morgan-Paisley K, Panos JJ, Kim EM, O'Hare E, Cleary JP, Lesne S, Ashe KH, Porritt M, Baker LE. Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures. Behav Brain Res. 2008;193:230–234.
    1. Calabrese B, Shaked GM, Tabarean IV, Braga J, Koo EH, Halpain S. Rapid, concurrent alterations in pre-and postsynaptic structure induced by naturally-secreted amyloid-beta protein. Mol Cell Neurosci. 2007;35:183–193.
    1. Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ. Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem Soc Trans. 2002;30:552–557.
    1. Walsh D, Klyubin I, Fadeeva J, William K, Cullen W, Anwyl R, Wolfe M, Rowan M, Selkoe D. Naturally secreted oligomers of the Alzheimer amyloid beta-protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–539.
    1. Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H, Wallin A, Lemere CA, Cullen WK, Peng Y, Wisniewski T, Selkoe DJ, Anwyl R, Walsh DM, Rowan MJ. Amyloid beta protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J Neurosci. 2008;28:4231–4237.
    1. Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R. Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J Neurosci. 2004;24:3370–3378.
    1. Walsh DM, Townsend M, Podlisny MB, Shankar GM, Fadeeva JV, Agnaf OE, Hartley DM, Selkoe DJ. Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation. J Neurosci. 2005;25:2455–2462.
    1. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27:2866–2875.
    1. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH. Natural oligomers, but not monomers, of the amyloid β-protein specifically disrupt the memory of learned behavior. Nature Neuroscience. 2005;8:79–84.
    1. Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ. Protofibrillar intermediates of amyloid β-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci. 1999;19:8876–8884.
    1. Wang HW, Pasternak JF, Kuo H, Ristic H, Lambert MP, Chromy B, Viola KL, Klein WL, Stine WB, Krafft GA, Trommer BL. Soluble oligomers of beta-amyloid(1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Research. 2002;924:133–140.
    1. Shrestha BR, Vitolo OV, Joshi P, Lordkipanidze T, Shelanski M, Dunaevsky A. Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons. Mol Cell Neurosci. 2006;33:274–282.
    1. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci. 2007;27:796–807.
    1. Walsh DM, Thulin E, Minogue AM, Gustavsson N, Pang E, Teplow DB, Linse S. A facile method for expression and purification of the Alzheimer's disease-associated amyloid beta-peptide. FEBS J. 2009;276:1266–1281.
    1. Harper JD, Wong SS, Lieber CM, Lansbury PT. Assembly of Aβ amyloid protofibrils: An in vitro model for a possible early event in Alzheimer's disease. Biochemistry. 1999;38:8972–8980.
    1. Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT Jr. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature. 2002;418:291.
    1. Isaacs AM, Senn DB, Yuan M, Shine JP, Yankner BA. Acceleration of amyloid beta-peptide aggregation by physiological concentrations of calcium. J Biol Chem. 2006;281:27916–27923.
    1. Hartley DM, Zhao C, Speier AC, Woodard GA, Li S, Li Z, Walz T. Transglutaminase induces protofibril-like amyloid beta-protein assemblies that are protease-resistant and inhibit long-term potentiation. J Biol Chem. 2008;283:16790–16800.
    1. Martins IC, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M, Jonckheere W, Van Gelder P, Hartmann D, D'Hooge R, De Strooper B, Schymkowitz J, Rousseau F. Lipids revert inert Abeta amyloid fibrils to neurotoxic protofibrils that affect learning in mice. EMBO J. 2008;27:224–233.
    1. Walsh DM, Lomakin A, Benedek GB, Maggio JE, Condron MM, Teplow DB. Amyloid β-protein fibrillogenesis: Detection of a protofibrillar intermediate. J Biol Chem. 1997;272:22364–22374.
    1. Nybo M, Svehag SE, Holm Nielsen E. An ultrastructural study of amyloid intermediates in A beta1-42 fibrillogenesis. Scand J Immunol. 1999;49:219–223.
    1. Hepler RW, Grimm KM, Nahas DD, Breese R, Dodson EC, Acton P, Keller PM, Yeager M, Wang H, Shughrue P, Kinney G, Joyce JG. Solution state characterization of amyloid beta-derived diffusible ligands. Biochemistry. 2006;45:15157–15167.
    1. Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009;457:1128–1132.
    1. Dahlgren KN, Manelli AM, Stine WB Jr, Baker LK, Krafft GA, LaDu MJ. Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability. J Biol Chem. 2002;277:32046–32053.
    1. Kim HJ, Chae SC, Lee DK, Chromy B, Lee SC, Park YC, Klein WL, Krafft GA, Hong ST. Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein. Faseb J. 2003;17:118–120.
    1. Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL. Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci. 2004;24:10191–10200.
    1. Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL. Alzheimer's disease-affected brain: presence of oligomeric Abeta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proceedings of the National Academy of Sciences (USA) 2003;100:10417–10422.
    1. Lambert MP, Viola KL, Chromy BA, Chang L, Morgan TE, Yu J, Venton DL, Krafft GA, Finch CE, Klein WL. Vaccination with soluble Abeta oligomers generates toxicity-neutralizing antibodies. J Neurochem. 2001;79:595–605.
    1. Chang L, Bakhos L, Wang ZG, Venton DL, Klein WL. Femtomole Immunodetection of synthetic and endogenous amyloid-b oligomers and its application to Alzheimer's disease drug candidate screening. Journal of Molecular Neuroscience. 2003;20:305–313.
    1. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science. 2003;300:486–489.
    1. Whalen BM, Selkoe DJ, Hartley DM. Small non-fibrillar assemblies of amyloid beta-protein bearing the Arctic mutation induce rapid neuritic degeneration. Neurobiol Dis. 2005;20:254–266.
    1. Maloney MT, Minamide LS, Kinley AW, Boyle JA, Bamburg JR. Beta-secretase-cleaved amyloid precursor protein accumulates at actin inclusions induced in neurons by stress or amyloid beta: a feedforward mechanism for Alzheimer's disease. J Neurosci. 2005;25:11313–11321.
    1. Kelly BL, Ferreira A. beta-Amyloid-induced dynamin 1 degradation is mediated by N-methyl-D-aspartate receptors in hippocampal neurons. J Biol Chem. 2006;281:28079–28089.
    1. Barghorn S, Zheng-Fischhofer Q, Ackmann M, Biernat J, von Bergen M, Mandelkow E. Structure, microtubule interactions, and paired helical filament aggregation by tau mutants of frontotemporal dementias [In Process Citation] Biochemistry. 2000;39:11714–11721.
    1. Deshpande A, Mina E, Glabe C, Busciglio J. Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci. 2006;26:6011–6018.
    1. Demuro A, Mina E, Kayed R, Milton SC, Parker I, Glabe CG. Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. J Biol Chem. 2005;280:17294–17300.
    1. Wogulis M, Wright S, Cunningham D, Chilcote T, Powell K, Rydel RE. Nucleation-dependent polymerization is an essential component of amyloid-mediated neuronal cell death. J Neurosci. 2005;25:1071–1080.
    1. White AR, Reyes R, Mercer JF, Camakaris J, Zheng H, Bush AI, Multhaup G, Beyreuther K, Masters CL, Cappai R. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Research. 1999;842:439–444.
    1. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005;8:1051–1058.
    1. Tamagno E, Bardini P, Guglielmotto M, Danni O, Tabaton M. The various aggregation states of beta-amyloid 1-42 mediate different effects on oxidative stress, neurodegeneration, and BACE-1 expression. Free Radic Biol Med. 2006;41:202–212.
    1. Zhao L, Ma QL, Calon F, Harris-White ME, Yang F, Lim GP, Morihara T, Ubeda OJ, Ambegaokar S, Hansen JE, Weisbart RH, Teter B, Frautschy SA, Cole GM. Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease. Nat Neurosci. 2006;9:234–242.
    1. Tomiyama T, Nagata T, Shimada H, Teraoka R, Fukushima A, Kanemitsu H, Takuma H, Kuwano R, Imagawa M, Ataka S, Wada Y, Yoshioka E, Nishizaki T, Watanabe Y, Mori H. A new amyloid beta variant favoring oligomerization in Alzheimer's-type dementia. Ann Neurol. 2008;63:377–387.
    1. Hung LW, Ciccotosto GD, Giannakis E, Tew DJ, Perez K, Masters CL, Cappai R, Wade JD, Barnham KJ. Amyloid-beta peptide (Abeta) neurotoxicity is modulated by the rate of peptide aggregation: Abeta dimers and trimers correlate with neurotoxicity. J Neurosci. 2008;28:11950–11958.
    1. Harmeier A, Wozny C, Rost BR, Munter LM, Hua H, Georgiev O, Beyermann M, Hildebrand PW, Weise C, Schaffner W, Schmitz D, Multhaup G. Role of amyloid-beta glycine 33 in oligomerization, toxicity, and neuronal plasticity. J Neurosci. 2009;29:7582–7590.
    1. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R. APP processing and synaptic function. Neuron. 2003;37:925–937.
    1. Brody DL, Magnoni S, Schwetye KE, Spinner ML, Esparza TJ, Stocchetti N, Zipfel GJ, Holtzman DM. Amyloid-beta dynamics correlate with neurological status in the injured human brain. Science. 2008;321:1221–1224.
    1. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S, Malinow R. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron. 2006;52:831–843.
    1. Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA. The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci. 2003;23:5531–5535.
    1. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, Palmeri A, Arancio O. Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008;28:14537–14545.
    1. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007;55:697–711.
    1. Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science. 2008;321:1686–1689.
    1. Spires TL, Meyer-Luehmann M, Stern EA, McLean PJ, Skoch J, Nguyen PT, Bacskai BJ, Hyman BT. Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci. 2005;25:7278–7287.
    1. Wang HY, Lee DH, Davis CB, Shank RP. Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors. J Neurochem. 2000;75:1155–1161.
    1. Dewachter I, Filipkowski RK, Priller C, Ris L, Neyton J, Croes S, Terwel D, Gysemans M, Devijver H, Borghgraef P, Godaux E, Kaczmarek L, Herms J, Van Leuven F. Deregulation of NMDA-receptor function and down-stream signaling in APP[V717I] transgenic mice. Neurobiol Aging. 2009;30:241–256.
    1. Yang SN, Tang YG, Zucker RS. Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. J Neurophysiol. 1999;81:781–787.
    1. Neveu D, Zucker RS. Postsynaptic levels of [Ca2+]i needed to trigger LTD and LTP. Neuron. 1996;16:619–629.
    1. Ye C, Walsh DM, Selkoe DJ, Hartley DM. Amyloid beta-protein induced electrophysiological changes are dependent on aggregation state: N-methyl-D-aspartate (NMDA) versus non-NMDA receptor/channel activation. Neurosci Lett. 2004;366:320–325.
    1. Snyder EM, Philpot BD, Huber KM, Dong X, Fallon JR, Bear MF. Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat Neurosci. 2001;4:1079–1085.
    1. Zakharenko SS, Zablow L, Siegelbaum SA. Altered presynaptic vesicle release and cycling during mGluR-dependent LTD. Neuron. 2002;35:1099–1110.
    1. O'Shea SD, Smith IM, McCabe OM, Walsh DM, O'Connor WT. Intracerebroventricular administration of amyloid β-protein oligomers selectively increases dorsal hippocampal dialysate glutamate levels in the awake rat. Sensors. 2008;8:7428–7437.
    1. Zhao WQ, De Felice FG, Fernandez S, Chen H, Lambert MP, Quon MJ, Krafft GA, Klein WL. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J. 2008;22:246–260.
    1. Lashuel HA, Hartley DM, Petre BM, Wall JS, Simon MN, Walz T, Lansbury PT Jr. Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid pores. J Mol Biol. 2003;332:795–808.
    1. Yu L, Edalji R, Harlan JE, Holzman TF, Lopez AP, Labkovsky B, Hillen H, Barghorn S, Ebert U, Richardson PL, Miesbauer L, Solomon L, Bartley D, Walter K, Johnson RW, Hajduk PJ, Olejniczak ET. Structural characterization of a soluble amyloid beta-peptide oligomer. Biochemistry. 2009;48:1870–1877.
    1. Barghorn S, Nimmrich V, Striebinger A, Krantz C, Keller P, Janson B, Bahr M, Schmidt M, Bitner RS, Harlan J, Barlow E, Ebert U, Hillen H. Globular amyloid beta-peptide oligomer-a homogenous and stable neuropathological protein in Alzheimer's disease. J Neurochem. 2005;95:834–847.
    1. Hermann D, Both M, Ebert U, Gross G, Schoemaker H, Draguhn A, Wicke K, Nimmrich V. Synaptic transmission is impaired prior to plaque formation in amyloid precursor protein-overexpressing mice without altering behaviorally-correlated sharp wave-ripple complexes. Neuroscience. 2009;162:1081–1090.
    1. 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 SI, Itokazu Y, Sato K, Takahashi H, Teplow DB, Nabeshima YI, Kakita A, Imahori K, Hoshi M. Isolation and characterization of patient-derived, toxic, high-mass amyloid {beta}-protein (A{beta}) assembly from Alzheimer's disease brains. J Biol Chem. 2009. pp. 32895–905.
    1. Hu NW, Smith IM, Walsh DM, Rowan MJ. Soluble amyloid-beta peptides potently disrupt hippocampal synaptic plasticity in the absence of cerebrovascular dysfunction in vivo. Brain. 2008;131:2414–2424.

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