{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:34:36Z","timestamp":1790422476049,"version":"4.1.0"},"reference-count":112,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AG065651"],"award-info":[{"award-number":["AG065651"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cerebral amyloid angiopathy (CAA), present in more than 90% of Alzheimer\u2019s disease (AD) cases, associates with focal ischemia and neurovascular dysfunction. Genetic variants at positions 21\u201323 of amyloid beta (A\u03b2), among them the Dutch mutation (A\u03b2E22Q), are primarily linked to CAA and the development of cerebral hemorrhages. An important contributor to CAA pathogenesis is the dysregulation of mitochondria-mediated pathways with concomitant induction of oxidative stress. Using biochemical assays and immunofluorescence microscopy, this work demonstrates the exacerbated formation of reactive oxygen species (ROS) in human brain microvascular endothelial cells after short exposure to soluble oligomers of synthetic homologues of A\u03b21-42 and the Dutch variant, inducing lipid peroxidation and protein carbonylation, both markers of oxidative stress. The heterogeneity of the soluble oligomeric assemblies inducing this oxidative response was highlighted by their reactivity with two conformational antibodies recognizing specific and mutually exclusive epitopes associated with either soluble prefibrillar oligomers or soluble fibrillar oligomers. Treatment with the multitarget antioxidants Trolox and methazolamide significantly attenuated the A\u03b2-mediated ROS production and reduced oxidative stress markers to basal levels. Our data highlight the damaging role of heterogeneous A\u03b2 oligomers and the preventing effect of antioxidants, suggesting ROS modulation as a complementary therapeutic strategy to preserve neurovascular unit integrity.<\/jats:p>","DOI":"10.3390\/antiox14111375","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T10:02:13Z","timestamp":1763546533000},"page":"1375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antioxidants Trolox and Methazolamide Protect Microvascular Endothelial Cells from Oxidative Damage Induced by Sporadic and Familial Forms of Oligomeric Amyloid-\u03b2"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5517-2772","authenticated-orcid":false,"given":"Maria Luisa","family":"Valle","sequence":"first","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bitseat","family":"Getaneh","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"William","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Ghiso","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agueda","family":"Rostagno","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00018-009-0182-4","article-title":"Cerebral amyloidosis: Amyloid subunits, mutants and phenotypes","volume":"67","author":"Rostagno","year":"2010","journal-title":"Cell. 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