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Despite these noteworthy findings, the molecular basis of the interaction between amyloid\u2010\u03b2 and tolcapone remains poorly understood, and the mechanisms by which tolcapone affects metal\u2013amyloid\u2010\u03b2 species have yet to be explored. In this work, we investigate the binding interactions of tolcapone with both copper\u2010free amyloid\u2010\u03b2 and copper\u2010associated amyloid\u2010\u03b2 complexes, using a combination of techniques including UV\u2013vis spectroscopy, circular dichroism, mass spectrometry, and surface plasmon resonance. The results reveal that tolcapone binds directly to amyloid\u2010\u03b2 monomers. Furthermore, in vitro assays confirm the capacity of tolcapone to act as a radical scavenger and to compete with amyloid\u2010\u03b2 for the binding of copper ions. Altogether, our findings suggest that tolcapone exerts a multifaceted protective effect, potentially inhibiting toxic metal\u2010free and metal aggregation pathways by preventing metal coordination to amyloid\u2010\u03b2 or disrupting preformed amyloid\u2010\u03b2\u2013metal complexes, thus offering new perspectives to explore and develop its analogs for the treatment of neurodegenerative disorders.<\/jats:p>","DOI":"10.1155\/bca\/1036276","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:55:13Z","timestamp":1772970913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tolcapone Interferes With Key Pathological Features in Alzheimer\u2019s 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