{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:01:54Z","timestamp":1789639314976,"version":"4.0.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of amyloid-beta (A\u03b2) aggregates, in the form of fibrils and plaques. While it has largely been stated that A\u03b2 oligomers are the main toxic species, significant evidence indicates that fibrils may also be relevant to AD pathogenesis. Notably, evidence indicates that while fibrils, through direct interaction with neuronal membranes, contribute to synaptic dysfunction and cellular damage, no direct evidence between fibrils and their impact on neuronal functions, including plasticity, was investigated. This study inquired into the impact of A\u03b2 fibrils complex on neuronal function and membrane integrity, shedding light on their contribution to synaptic defects. A\u03b2 fibrils were generated from A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    oligomers, and their effects were evaluated on synaptic plasticity in ex vivo hippocampal slices from both female and male mice. Compared to A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    oligomers, fibrils induced more severe damage in synaptic plasticity, emphasizing their potent neurotoxicity effect underlying cognitive decline. Additionally, using a liposomal model to examine fibril-membrane interactions, it was observed that A\u03b2 fibrils are able to affect membrane fluidity compared to the A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    oligomeric species, indicating that the size and aggregation state of A\u03b2 fibrils are crucial for their toxicity. These findings challenge the view that oligomers are the primary toxic species in AD, showing that A\u03b2 fibrils also play an active role in cellular dysfunction, promoting a synaptic dysfunction correlated to the cognitive impairment observed in AD.\n                  <\/jats:p>","DOI":"10.1038\/s41401-026-01808-7","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T02:10:52Z","timestamp":1781230252000},"page":"2820-2828","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amyloid-beta fibrils as active contributors to synaptic dysfunction in Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"47","author":[{"given":"Nunzia","family":"Maisto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Ciufolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Dashtiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Casoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almerinda","family":"Di Venere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Mango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"1808_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimer\u2019s Dement. 2018;14:535\u201362.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1808_CR2","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","volume":"298","author":"DJ Selkoe","year":"2002","unstructured":"Selkoe DJ. Alzheimer\u2019s disease is a synaptic failure. Science. 2002;298:789\u201391.","journal-title":"Science"},{"key":"1808_CR3","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer\u2019s disease at 25 years. EMBO Mol Med. 2016;8:595\u2013608.","journal-title":"EMBO Mol Med"},{"key":"1808_CR4","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fnins.2015.00186","volume":"9","author":"D Zhu","year":"2015","unstructured":"Zhu D, Bungart BL, Yang X, Zhumadilov Z, Lee JC-M, Askarova S. Role of membrane biophysics in Alzheimer\u2019s-related cell pathways. Front Neurosci. 2015;9:186.","journal-title":"Front Neurosci"},{"key":"1808_CR5","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1126\/science.aao2825","volume":"358","author":"L Gremer","year":"2017","unstructured":"Gremer L, Sch\u00f6lzel D, Schenk C, Reinartz E, Labahn J, Ravelli RBG, et al. Fibril structure of amyloid-\u03b2(1\u201342) by cryo\u2013electron microscopy. Science. 2017;358:116\u20139.","journal-title":"Science"},{"key":"1808_CR6","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1021\/bi051952q","volume":"45","author":"AT Petkova","year":"2006","unstructured":"Petkova AT, Yau W-M, Tycko R. Experimental constraints on quaternary structure in Alzheimer\u2019s \u03b2-amyloid fibrils. Biochemistry. 2006;45:498\u2013512.","journal-title":"Biochemistry"},{"key":"1808_CR7","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.neuron.2015.03.017","volume":"86","author":"R Tycko","year":"2015","unstructured":"Tycko R. Amyloid polymorphism: structural basis and neurobiological relevance. Neuron. 2015;86:632\u201345.","journal-title":"Neuron"},{"key":"1808_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.neurobiolaging.2018.06.025","volume":"71","author":"W Gulisano","year":"2018","unstructured":"Gulisano W, Melone M, Li Puma DD, Tropea MR, Palmeri A, Arancio O, et al. The effect of amyloid-\u03b2 peptide on synaptic plasticity and memory is influenced by different isoforms, concentrations, and aggregation status. Neurobiol Aging. 2018;71:51\u201360.","journal-title":"Neurobiol Aging"},{"key":"1808_CR9","doi-asserted-by":"publisher","first-page":"9220","DOI":"10.1096\/fj.201900604R","volume":"33","author":"T Yasumoto","year":"2019","unstructured":"Yasumoto T, Takamura Y, Tsuji M, Watanabe-Nakayama T, Imamura K, Inoue H, et al. High molecular weight amyloid \u03b21-42 oligomers induce neurotoxicity via plasma membrane damage. FASEB J. 2019;33:9220\u201334.","journal-title":"FASEB J"},{"key":"1808_CR10","doi-asserted-by":"publisher","first-page":"14537","DOI":"10.1523\/JNEUROSCI.2692-08.2008","volume":"28","author":"D Puzzo","year":"2008","unstructured":"Puzzo D, Privitera L, Leznik E, F\u00e0 M, Staniszewski A, Palmeri A, et al. Picomolar amyloid-\u03b2 positively modulates synaptic plasticity and memory in hippocampus. J Neurosci. 2008;28:14537\u201345.","journal-title":"J Neurosci"},{"key":"1808_CR11","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.3390\/biomedicines11051411","volume":"11","author":"TG Schreiner","year":"2023","unstructured":"Schreiner TG, Schreiner OD, Adam M, Popescu BO. The roles of the amyloid beta monomers in physiological and pathological conditions. Biomedicines. 2023;11:1411.","journal-title":"Biomedicines"},{"key":"1808_CR12","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.neurobiolaging.2009.04.005","volume":"32","author":"I Klyubin","year":"2011","unstructured":"Klyubin I, Wang Q, Reed MN, Irving EA, Upton N, Hofmeister J, et al. Protection against A\u03b2-mediated rapid disruption of synaptic plasticity and memory by memantine. Neurobiol Aging. 2011;32:614\u201323.","journal-title":"Neurobiol Aging"},{"key":"1808_CR13","doi-asserted-by":"crossref","unstructured":"Mango D, Weisz F, Nistic\u00f2 R. Ginkgolic acid protects against A\u03b2-induced synaptic dysfunction in the hippocampus. Front Pharmacol. 2016;7:401.","DOI":"10.3389\/fphar.2016.00401"},{"key":"1808_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-024-03019-2","volume":"14","author":"G Piccioni","year":"2024","unstructured":"Piccioni G, Maisto N, d\u2019Ettorre A, Strimpakos G, Nistic\u00f2 R, Triaca V, et al. Switch to phagocytic microglia by CSFR1 inhibition drives amyloid-beta clearance from glutamatergic terminals rescuing LTP in acute hippocampal slices. Transl Psychiatry. 2024;14:338.","journal-title":"Transl Psychiatry"},{"key":"1808_CR15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.phrs.2018.03.016","volume":"131","author":"D Mango","year":"2018","unstructured":"Mango D, Nistic\u00f2 R. Role of ASIC1a in A\u03b2-induced synaptic alterations in the hippocampus. Pharmacol Res. 2018;131:61\u20135.","journal-title":"Pharmacol Res"},{"key":"1808_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.151133","volume":"742","author":"J Arriagada","year":"2025","unstructured":"Arriagada J, Mercer\u00f3n D, Ardiles \u00c1, Mu\u00f1oz P, Paula-Lima A. Excitatory-inhibitory synaptic imbalance induced by acute intra-hippocampus injections of amyloid-\u03b2 oligomers. Biochem Biophys Res Commun. 2025;742:151133.","journal-title":"Biochem Biophys Res Commun"},{"key":"1808_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109786","volume":"37","author":"JL Sanderson","year":"2021","unstructured":"Sanderson JL, Freund RK, Gorski JA, Dell\u2019Acqua ML. \u03b2-Amyloid disruption of LTP\/LTD balance is mediated by AKAP150-anchored PKA and calcineurin regulation of Ca2+-permeable AMPA receptors. Cell Rep. 2021;37:109786.","journal-title":"Cell Rep"},{"key":"1808_CR18","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nn.3028","volume":"15","author":"I Benilova","year":"2012","unstructured":"Benilova I, Karran E, De Strooper B. The toxic A\u03b2 oligomer and Alzheimer\u2019s disease: an emperor in need of clothes. Nat Neurosci. 2012;15:349\u201357.","journal-title":"Nat Neurosci"},{"key":"1808_CR19","doi-asserted-by":"publisher","first-page":"179","DOI":"10.2174\/156720506777632871","volume":"3","author":"D Puzzo","year":"2006","unstructured":"Puzzo D, Arancio O. Fibrillar beta-amyloid impairs the late phase of long term potentiation. Curr Alzheimer Res. 2006;3:179\u201383.","journal-title":"Curr Alzheimer Res"},{"key":"1808_CR20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26991","volume":"6","author":"D Puzzo","year":"2017","unstructured":"Puzzo D, Piacentini R, F\u00e1 M, Gulisano W, Li Puma DD, Staniszewski A, et al. LTP and memory impairment caused by extracellular A\u03b2 and Tau oligomers is APP-dependent. eLife. 2017;6:e26991.","journal-title":"eLife"},{"key":"1808_CR21","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/nrm3810","volume":"15","author":"TPJ Knowles","year":"2014","unstructured":"Knowles TPJ, Vendruscolo M, Dobson CM. The amyloid state and its association with protein misfolding diseases. Nat Rev Mol Cell Biol. 2014;15:384\u201396.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1808_CR22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s42254-023-00598-9","volume":"5","author":"TCT Michaels","year":"2023","unstructured":"Michaels TCT, Qian D, \u0160ari\u0107 A, Vendruscolo M, Linse S, Knowles TPJ. Amyloid formation as a protein phase transition. Nat Rev Phys. 2023;5:379\u201397.","journal-title":"Nat Rev Phys"},{"key":"1808_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2024.103949","volume":"130","author":"M Johannesson","year":"2024","unstructured":"Johannesson M, S\u00f6derberg L, Zachrisson O, Fritz N, Kylefjord H, Gkanatsiou E, et al. Lecanemab demonstrates highly selective binding to A\u03b2 protofibrils isolated from Alzheimer\u2019s disease brains. Mol Cell Neurosci. 2024;130:103949.","journal-title":"Mol Cell Neurosci"},{"key":"1808_CR24","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1177\/0271678X20943823","volume":"40","author":"N Percie Du Sert","year":"2020","unstructured":"Percie Du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research*. J Cereb Blood Flow Metab. 2020;40:1769\u201377.","journal-title":"J Cereb Blood Flow Metab"},{"key":"1808_CR25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2174\/157015907780077105","volume":"5","author":"S Cho","year":"2007","unstructured":"Cho S, Wood A, Bowlby M. Brain slices as models for neurodegenerative disease and screening platforms to identify novel therapeutics. CN. 2007;5:19\u201333.","journal-title":"CN"},{"key":"1808_CR26","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671\u20135.","journal-title":"Nat Methods"},{"key":"1808_CR27","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1096\/fj.09-141390","volume":"24","author":"E Dainese","year":"2010","unstructured":"Dainese E, Angelucci CB, Sabatucci A, De Filippis V, Mei G, Maccarrone M. A novel role for iron in modulating the activity and membrane-binding ability of a trimmed soybean lipoxygenase-1. FASEB J. 2010;24:1725\u201336.","journal-title":"FASEB J"},{"key":"1808_CR28","doi-asserted-by":"publisher","first-page":"9234","DOI":"10.1021\/bi800638v","volume":"47","author":"G Mei","year":"2008","unstructured":"Mei G, Di Venere A, Nicolai E, Angelucci CB, Ivanov I, Sabatucci A, et al. Structural properties of plant and mammalian lipoxygenases. Temperature-dependent conformational alterations and membrane binding ability. Biochemistry. 2008;47:9234\u201342.","journal-title":"Biochemistry"},{"key":"1808_CR29","doi-asserted-by":"publisher","first-page":"6007","DOI":"10.3390\/ijms23116007","volume":"23","author":"A Nucara","year":"2022","unstructured":"Nucara A, Ripanti F, Sennato S, Nisini G, De Santis E, Sefat M, et al. Influence of cortisol on the fibril formation kinetics of A\u03b242 peptide: a multi-technical approach. IJMS. 2022;23:6007.","journal-title":"IJMS"},{"key":"1808_CR30","doi-asserted-by":"publisher","first-page":"9758","DOI":"10.1073\/pnas.1218402110","volume":"110","author":"SIA Cohen","year":"2013","unstructured":"Cohen SIA, Linse S, Luheshi LM, Hellstrand E, White DA, Rajah L, et al. Proliferation of amyloid-\u03b242 aggregates occurs through a secondary nucleation mechanism. Proc Natl Acad Sci USA. 2013;110:9758\u201363.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1808_CR31","doi-asserted-by":"publisher","first-page":"7443","DOI":"10.1073\/pnas.0812033106","volume":"106","author":"AK Paravastu","year":"2009","unstructured":"Paravastu AK, Qahwash I, Leapman RD, Meredith SC, Tycko R. Seeded growth of \u03b2-amyloid fibrils from Alzheimer\u2019s brain-derived fibrils produces a distinct fibril structure. Proc Natl Acad Sci USA. 2009;106:7443\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1808_CR32","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3390\/biophysica2020010","volume":"2","author":"D Shea","year":"2022","unstructured":"Shea D, Daggett V. Amyloid-\u03b2 oligomers: multiple moving targets. Biophysica. 2022;2:91\u2013110.","journal-title":"Biophysica"},{"key":"1808_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202200086","volume":"44","author":"A Bigi","year":"2022","unstructured":"Bigi A, Cascella R, Chiti F, Cecchi C. Amyloid fibrils act as a reservoir of soluble oligomers, the main culprits in protein deposition diseases. BioEssays. 2022;44:2200086.","journal-title":"BioEssays"},{"key":"1808_CR34","doi-asserted-by":"publisher","first-page":"16024","DOI":"10.1021\/acs.langmuir.9b02484","volume":"35","author":"CM Vander Zanden","year":"2019","unstructured":"Vander Zanden CM, Wampler L, Bowers I, Watkins EB, Majewski J, Chi EY. Fibrillar and nonfibrillar amyloid beta structures drive two modes of membrane-mediated toxicity. Langmuir. 2019;35:16024\u201336.","journal-title":"Langmuir"},{"key":"1808_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.178317","volume":"1008","author":"N Maisto","year":"2025","unstructured":"Maisto N, Dashtiani S, Forte J, Ammendolia MG, Triaca V, Rinaldi F, et al. Ellagic acid-loaded nanovesicles rescue LTP impairment and neuroinflammation in an AD ex-vivo model. Eur J Pharmacol. 2025;1008:178317.","journal-title":"Eur J Pharmacol"},{"key":"1808_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2021.116141","volume":"334","author":"S Andrade","year":"2021","unstructured":"Andrade S, Ramalho MJ, Loureiro JA, Pereira MC. Liposomes as biomembrane models: Biophysical techniques for drug-membrane interaction studies. J Mol Liq. 2021;334:116141.","journal-title":"J Mol Liq"},{"key":"1808_CR37","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1016\/S0006-3495(90)82637-0","volume":"57","author":"T Parasassi","year":"1990","unstructured":"Parasassi T, De Stasio G, d\u2019Ubaldo A, Gratton E. Phase fluctuation in phospholipid membranes revealed by Laurdan fluorescence. Biophys J. 1990;57:1179\u201386.","journal-title":"Biophys J"},{"key":"1808_CR38","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nprot.2011.419","volume":"7","author":"DM Owen","year":"2012","unstructured":"Owen DM, Rentero C, Magenau A, Abu-Siniyeh A, Gaus K. Quantitative imaging of membrane lipid order in cells and organisms. Nat Protoc. 2012;7:24\u201335.","journal-title":"Nat Protoc"},{"key":"1808_CR39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.4103\/0972-2327.144284","volume":"18","author":"M Verma","year":"2015","unstructured":"Verma M, Vats A, Taneja V. Toxic species in amyloid disorders: oligomers or mature fibrils. Ann Indian Acad Neurol. 2015;18:138\u201345.","journal-title":"Ann Indian Acad Neurol"},{"key":"1808_CR40","doi-asserted-by":"crossref","unstructured":"Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG. Soluble amyloid-\u03b2 oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease. Front Cell Neurosci. 2015;9:191.","DOI":"10.3389\/fncel.2015.00191"},{"key":"1808_CR41","doi-asserted-by":"crossref","unstructured":"Nygaard HB, Strittmatter SM. Cellular Prion protein mediates the toxicity of \u03b2-amyloid oligomers: implications for Alzheimer disease. Arch Neurol. 2009;66:1325\u20138.","DOI":"10.1001\/archneurol.2009.223"},{"key":"1808_CR42","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1111\/j.1742-4658.2010.07568.x","volume":"277","author":"M Sakono","year":"2010","unstructured":"Sakono M, Zako T. Amyloid oligomers: formation and toxicity of A\u03b2 oligomers. FEBS J. 2010;277:1348\u201358.","journal-title":"FEBS J"},{"key":"1808_CR43","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrm2101","volume":"8","author":"C Haass","year":"2007","unstructured":"Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer\u2019s amyloid \u03b2-peptide. Nat Rev Mol Cell Biol. 2007;8:101\u201312.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1808_CR44","doi-asserted-by":"publisher","first-page":"20","DOI":"10.4161\/pri.4.1.11378","volume":"4","author":"W-F Xue","year":"2010","unstructured":"Xue W-F, Hellewell AL, Hewitt EW, Radford SE. Fibril fragmentation in amyloid assembly and cytotoxicity: When size matters. Prion. 2010;4:20\u20135.","journal-title":"Prion"},{"key":"1808_CR45","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1083\/jcb.201104133","volume":"195","author":"A Demuro","year":"2011","unstructured":"Demuro A, Smith M, Parker I. Single-channel Ca2+ imaging implicates A\u03b21-42 amyloid pores in Alzheimer\u2019s disease pathology. J Cell Biol. 2011;195:515\u201324.","journal-title":"J Cell Biol."},{"key":"1808_CR46","doi-asserted-by":"publisher","first-page":"13300","DOI":"10.1021\/ja103725c","volume":"132","author":"B Strodel","year":"2010","unstructured":"Strodel B, Lee JWL, Whittleston CS, Wales DJ. Transmembrane structures for Alzheimer\u2019s A\u03b21\u221242\u00a0oligomers. J Am Chem Soc. 2010;132:13300\u201312.","journal-title":"J Am Chem Soc"},{"key":"1808_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16566-1","volume":"11","author":"S Ciudad","year":"2020","unstructured":"Ciudad S, Puig E, Botzanowski T, Meigooni M, Arango AS, Do J, et al. A\u03b2(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage. Nat Commun. 2020;11:3014.","journal-title":"Nat Commun"},{"key":"1808_CR48","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.tibs.2015.10.002","volume":"40","author":"KW Tipping","year":"2015","unstructured":"Tipping KW, Van Oosten-Hawle P, Hewitt EW, Radford SE. Amyloid fibres: inert end-stage aggregates or key players in disease?. Trends Biochem Sci. 2015;40:719\u201327.","journal-title":"Trends Biochem Sci"},{"key":"1808_CR49","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/361031a0","volume":"361","author":"TVP Bliss","year":"1993","unstructured":"Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31\u20139.","journal-title":"Nature"},{"key":"1808_CR50","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ebiom.2016.03.035","volume":"6","author":"U Sengupta","year":"2016","unstructured":"Sengupta U, Nilson AN, Kayed R. The role of amyloid-\u03b2 oligomers in toxicity, propagation, and immunotherapy. EBioMedicine. 2016;6:42\u20139.","journal-title":"EBioMedicine"},{"key":"1808_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-08186-8","volume":"17","author":"AA Abdulkhaliq","year":"2026","unstructured":"Abdulkhaliq AA, Kim B, Almoghrabi YM, Khan J, Ajoolabady A, Ren J, et al. Amyloid-\u03b2 and Tau in Alzheimer\u2019s disease: pathogenesis, mechanisms, and interplay. Cell Death Dis. 2026;17:21.","journal-title":"Cell Death Dis"},{"key":"1808_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-025-00610-1","volume":"11","author":"K Rabiei","year":"2025","unstructured":"Rabiei K, Petrella JR, Lenhart S, Liu C, Hao W. For the Alzheimer Disease Neuroimaging Initiative. Data-driven modeling of amyloid-\u03b2 targeted antibodies for Alzheimer\u2019s disease. Npj Syst Biol Appl. 2025;11:134.","journal-title":"Npj Syst Biol Appl"},{"key":"1808_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1645952","volume":"19","author":"NG Metzendorf","year":"2025","unstructured":"Metzendorf NG, Sehlin D, Hultqvist G. Key considerations for ELISA-based quantification of diverse amyloid beta forms in murine brain homogenates. Front Neurosci. 2025;19:1645952.","journal-title":"Front Neurosci"},{"key":"1808_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3416","volume":"4","author":"AJ Nicoll","year":"2013","unstructured":"Nicoll AJ, Panico S, Freir DB, Wright D, Terry C, Risse E, et al. Amyloid-\u03b2 nanotubes are associated with prion protein-dependent synaptotoxicity. Nat Commun. 2013;4:2416.","journal-title":"Nat Commun"},{"key":"1808_CR55","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/j.procbio.2016.05.015","volume":"51","author":"SK Chaturvedi","year":"2016","unstructured":"Chaturvedi SK, Siddiqi MK, Alam P, Khan RH. Protein misfolding and aggregation: mechanism, factors and detection. Process Biochem. 2016;51:1183\u201392.","journal-title":"Process Biochem"},{"key":"1808_CR56","doi-asserted-by":"publisher","first-page":"4499","DOI":"10.1021\/bi602461y","volume":"46","author":"ACM Ferreon","year":"2007","unstructured":"Ferreon ACM, Deniz AA. \u03b1-synuclein multistate folding thermodynamics: implications for protein misfolding and aggregation. Biochemistry. 2007;46:4499\u2013509.","journal-title":"Biochemistry"},{"key":"1808_CR57","doi-asserted-by":"publisher","first-page":"11361","DOI":"10.1021\/bi048864a","volume":"43","author":"D Foguel","year":"2004","unstructured":"Foguel D, Silva JL. New insights into the mechanisms of protein misfolding and aggregation in amyloidogenic diseases derived from pressure studies. Biochemistry. 2004;43:11361\u201370.","journal-title":"Biochemistry"},{"key":"1808_CR58","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.jmb.2008.07.072","volume":"382","author":"T Okada","year":"2008","unstructured":"Okada T, Ikeda K, Wakabayashi M, Ogawa M, Matsuzaki K. Formation of toxic A\u03b21\u201340 fibrils on GM1 ganglioside-containing membranes mimicking lipid rafts: polymorphisms in A\u03b21\u201340 fibrils. J Mol Biol. 2008;382:1066\u201374.","journal-title":"J Mol Biol"},{"key":"1808_CR59","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1042\/BJ20110750","volume":"439","author":"TL Williams","year":"2011","unstructured":"Williams TL, Johnson BRG, Urbanc B, Jenkins ATA, Connell SDA, Serpell LC. A\u03b242 oligomers, but not fibrils, simultaneously bind to and cause damage to ganglioside-containing lipid membranes. Biochem J. 2011;439:67\u201377.","journal-title":"Biochem J"},{"key":"1808_CR60","doi-asserted-by":"publisher","first-page":"226","DOI":"10.3389\/fnagi.2018.00226","volume":"10","author":"EJ Fern\u00e1ndez-P\u00e9rez","year":"2018","unstructured":"Fern\u00e1ndez-P\u00e9rez EJ, Sep\u00falveda FJ, Peters C, Bascu\u00f1\u00e1n D, Riffo-Lepe NO, Gonz\u00e1lez-Sanmiguel J, et al. Effect of cholesterol on membrane fluidity and association of A\u03b2 oligomers and subsequent neuronal damage: a double-edged sword. Front Aging Neurosci. 2018;10:226.","journal-title":"Front Aging Neurosci"},{"key":"1808_CR61","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1111\/j.1471-4159.2010.06997.x","volume":"116","author":"M Ogawa","year":"2011","unstructured":"Ogawa M, Tsukuda M, Yamaguchi T, Ikeda K, Okada T, Yano Y, et al. Ganglioside-mediated aggregation of amyloid \u03b2-proteins (A\u03b2): comparison between A\u03b2-(1\u201342) and A\u03b2-(1\u201340). J Neurochem. 2011;116:851\u20137.","journal-title":"J Neurochem"},{"key":"1808_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/735206","volume":"2012","author":"E Ferreiro","year":"2012","unstructured":"Ferreiro E, Baldeiras I, Ferreira IL, Costa RO, Rego AC, Pereira CF, et al. Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer\u2019s disease: from pathogenesis to biomarkers. Int J Cell Biol. 2012;2012:1\u201323.","journal-title":"Int J Cell Biol"},{"key":"1808_CR63","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.3389\/fnins.2019.01444","volume":"13","author":"E Llanos-Gonz\u00e1lez","year":"2020","unstructured":"Llanos-Gonz\u00e1lez E, Henares-Chavarino \u00c1A, Pedrero-Prieto CM, Garc\u00eda-Carpintero S, Fronti\u00f1\u00e1n-Rubio J, Sancho-Bielsa FJ, et al. Interplay between mitochondrial oxidative disorders and proteostasis in Alzheimer\u2019s disease. Front Neurosci. 2020;13:1444.","journal-title":"Front Neurosci"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01808-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01808-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01808-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:02:47Z","timestamp":1789635767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41401-026-01808-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":63,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["1808"],"URL":"https:\/\/doi.org\/10.1038\/s41401-026-01808-7","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"7 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}