The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade

Journal of Alzheimer's Disease : JAD
Erika N ClineWilliam L Klein

Abstract

The amyloid-β oligomer (AβO) hypothesis was introduced in 1998. It proposed that the brain damage leading to Alzheimer's disease (AD) was instigated by soluble, ligand-like AβOs. This hypothesis was based on the discovery that fibril-free synthetic preparations of AβOs were potent CNS neurotoxins that rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998). The mechanism was attributed to disrupted signaling involving the tyrosine-protein kinase Fyn, mediated by an unknown toxin receptor. Over 4,000 articles concerning AβOs have been published since then, including more than 400 reviews. AβOs have been shown to accumulate in an AD-dependent manner in human and animal model brain tissue and, experimentally, to impair learning and memory and instigate major facets of AD neuropathology, including tau pathology, synapse deterioration and loss, inflammation, and oxidative damage. As reviewed by Hayden and Teplow in 2013, the AβO hypothesis "has all but supplanted the amyloid cascade." Despite the emerging understanding of the role played by AβOs in AD pathogenesis, AβOs have not yet received the clinical attention given to amyloid plaques, which have been at the core of major...Continue Reading

References

Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Nov 1, 1994·Journal of Neuropathology and Experimental Neurology·J FrackowiakH M Wisniewski
Nov 15, 1994·Biochemical and Biophysical Research Communications·T OdaC E Finch
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·N ArispeE Rojas
Apr 7, 1997·The Journal of Experimental Medicine·D QianA Weiss
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P LambertW L Klein
Jul 14, 1998·Nature Medicine·C GeulaB A Yankner
Sep 16, 2000·Science·S Mouillet-RichardO Kellermann
Dec 22, 2000·Neurobiology of Aging·C SchultzH Braak
Mar 16, 2001·Trends in Neurosciences·W L KleinC E Finch
Nov 9, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hyeon-Jin KimSeong-Tshool Hong
Aug 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yuesong GongWilliam L Klein
Nov 5, 2003·Biochemistry·Brett A ChromyWilliam L Klein
Dec 4, 2003·Neurobiology of Aging·Salvatore OddoFrank M LaFerla
Mar 6, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gloria LeeHanna Ksiezak-Reding
Mar 12, 2004·The Journal of Membrane Biology·N Arispe
May 14, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jeannie ChinLennart Mucke
May 26, 2004·Lancet Neurology·Laura FratiglioniBengt Winblad
May 29, 2004·The Journal of Biological Chemistry·Shin-Young ParkShalom Avraham
Nov 3, 2004·Analytical Biochemistry·Harry LeVine
Nov 13, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascale N LacorWilliam L Klein
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Feb 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Dimitra G GeorganopoulouChad A Mirkin
Apr 29, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Paul A AdlardCarl W Cotman
Jul 14, 2005·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Gal BitanDavid B Teplow
Jul 19, 2005·Nature Neuroscience·Eric M SnyderPaul Greengard

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Citations

Sep 25, 2018·European Journal of Clinical Investigation·Sally HunterCarol Brayne
Nov 8, 2018·Journal of Alzheimer's Disease : JAD·Patricia LlorenteMaría J Bullido
Jun 19, 2019·Nanoscale·Sibaprasad Maity, Yuri L Lyubchenko
Feb 15, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Rudy J CastellaniGeorge Perry
Jan 31, 2019·Molecular Pharmacology·Elena PopugaevaIlya Bezprozvanny
Oct 2, 2019·The FEBS Journal·Tohidul IslamAnders Olofsson
Jan 1, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·De-Yang SunWei-Shuo Fang
Dec 10, 2019·Current Pharmaceutical Design·Giuseppe CarusoSara Merlo
Oct 30, 2019·Critical Reviews in Clinical Laboratory Sciences·Bhavana VeerabhadrappaSylvain Lehmann
Nov 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·You ZhouQingyou Xia
Nov 11, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Martin TolarMarwan Sabbagh
Feb 19, 2020·Current Pharmaceutical Design·Miren EttchetoAntoni Camins
Jul 8, 2020·Chemical Society Reviews·Pu Chun KeRaffaele Mezzenga
Feb 1, 2020·Current Neuropharmacology·Sara MerloMaria Angela Sortino
Jun 23, 2020·Protein Science : a Publication of the Protein Society·Jacques FantiniNouara Yahi
Apr 24, 2020·Current Topics in Medicinal Chemistry·Md Tanvir KabirGhulam Md Ashraf
Aug 1, 2020·Frontiers in Cell and Developmental Biology·Elena V MitroshinaMaria V Vedunova
Sep 26, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Xu-Qiao ChenWilliam C Mobley
Dec 12, 2018·Frontiers in Aging Neuroscience·Honghua ZhengYun-Wu Zhang
Jun 13, 2019·Molecular Neurodegeneration·Daniel Twohig, Henrietta M Nielsen
Nov 19, 2019·Frontiers in Aging Neuroscience·Puneet TalwarRachna Agarwal
Oct 15, 2019·Frontiers in Aging Neuroscience·Laura García-GonzálezSantiago Rivera
Mar 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lindsay A WelikovitchA Claudio Cuello
Sep 13, 2020·Membranes·Vladimir Rudajev, Jiri Novotny
Sep 12, 2020·Biomarker Insights·Elena CamporesiHenrik Zetterberg
Sep 30, 2018·Journal of Molecular Neuroscience : MN·Nalini Vijay Gorantla, Subashchandrabose Chinnathambi
Aug 16, 2019·Acta Neuropathologica·Luis Aragão GomesDietmar Rudolf Thal

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Methods Mentioned

BETA
transgenic
atomic force microscopy
size exclusion chromatography
AFM
GTPase
immunoprecipitation
BACE

Software Mentioned

PICUP

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