{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:06:53Z","timestamp":1773662813081,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,12]]},"group-title":"Neuroscience","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute On Aging of the National Institutes of Health","award":["R01AG078187"],"award-info":[{"award-number":["R01AG078187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Amyloid plaques are a hallmark of Alzheimer\u2019s disease (AD) progression; however, the early stages of plaque formation and the specific amyloid-beta (A\u03b2) species involved remain difficult to study. While post-mortem tissue provides insight into end-stage mature plaques, therapeutic development requires targeting the earliest A\u03b2 oligomers to arrest plaque formation. Furthermore, inherently toxic soluble A\u03b2 oligomers off-pathway from plaque formation are implicated as a driving force of AD pathology. It also remains unclear if the specific nature of key disease-relevant species can be accurately replicated in preparations of synthetic peptides.. To bridge this gap, we utilize brain organoids carrying AD mutations as a biologically authentic source for A\u03b2 peptides and oligomers. We demonstrate that these mutations do not disrupt organoid development and that the resulting conditioned media contains A\u03b2 oligomers with disease-relevant structures. Finally, we show that these oligomers can be concentrated and segregated via differential ultracentrifugation for further experimental applications.<\/jats:p>","DOI":"10.64898\/2026.03.09.710594","type":"posted-content","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:40:16Z","timestamp":1773337216000},"source":"Crossref","is-referenced-by-count":0,"title":["Alzheimer\u2019s Disease Brain Organoids as a Source of Disease-Relevant Amyloid-Beta Oligomers"],"prefix":"10.64898","author":[{"given":"Eric","family":"Zanderigo","sequence":"first","affiliation":[{"name":"Department of Chemistry, Wesleyan University, Middletown, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manaal","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Biology, Wesleyan University, Middletown, CT, 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