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Resveratrol, a natural polyphenol, has been proposed as an inhibitor of A\u03b2 aggregation, but its mechanistic effects across distinct A\u03b242 aggregates remain unresolved. To better evaluate resveratrol's potential to treat AD, here we focus on molecular\u2010level insights into the mechanisms that underlie its interaction with several distinct classes of A\u03b242 aggregates. In contrast to published approaches that are based on monitoring the evolution of the total fibrillar mass, we employ time\u2010resolved in situ atomic force microscopy to explore the effects of resveratrol on A\u03b242 amyloid and non\u2010amyloid assemblies. While data suggest a weak interaction between resveratrol and low\u2010molecular\u2010weight A\u03b242 species, we also observe a concentration\u2010dependent reduction in fibrillization. In the presence of resveratrol, we observe a decrease in fibril thickness and end\u2010dependent slowing of elongation; furthermore, the fibrils exhibit reduced mechanical integrity and fragment under minimal scanning stress. Importantly, resveratrol does not affect the formation or morphology of oligomers and amorphous aggregates. These findings suggest that resveratrol selectively targets the fibril pathway while leaving oligomeric assemblies unaltered. The results provide mechanistic insights into the differential effects of small molecules on A\u03b242 assemblies and establish a framework for evaluating inhibitors of aggregation with single\u2010aggregate resolution.<\/jats:p>","DOI":"10.1002\/adbi.202500586","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:01:43Z","timestamp":1772989303000},"source":"Crossref","is-referenced-by-count":1,"title":["Differential Responses of Amyloid\u2010\u03b2 42 Aggregates to Resveratrol"],"prefix":"10.1002","volume":"10","author":[{"given":"Nghia D.","family":"Nguyen","sequence":"first","affiliation":[{"name":"William A. Brookshire Department of Chemical and Biomolecular Engineering University of Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-8720","authenticated-orcid":false,"given":"Peter G.","family":"Vekilov","sequence":"additional","affiliation":[{"name":"William A. 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