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Herrmann","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Zina Stern Postdoctoral Fellowship","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/100007109","name":"May and Samuel Rudin Family Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007109","id-type":"DOI","asserted-by":"publisher"}]},{"name":"William J and Pam Michaelcheck","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,4,23]]},"abstract":"<jats:p>Proteinaceous brain inclusions, neuroinflammation, and vascular dysfunction are common pathologies in Alzheimer\u2019s disease (AD). Vascular deficits include a compromised blood\u2013brain barrier, which can lead to extravasation of blood proteins like fibrinogen into the brain. Fibrinogen\u2019s interaction with the amyloid-beta (A\u03b2) peptide is known to worsen thrombotic and cerebrovascular pathways in AD. Lecanemab, an FDA-approved antibody therapy for AD, clears A\u03b2 plaque from the brain and slows cognitive decline. Here, we show that lecanemab blocks fibrinogen\u2019s binding to A\u03b2 protofibrils, preventing A\u03b2\/fibrinogen-mediated delayed fibrinolysis and clot abnormalities in vitro and in human plasma. Additionally, we show that lecanemab dissociates the A\u03b2\/fibrinogen complex and prevents fibrinogen from exacerbating A\u03b2-induced synaptotoxicity in mouse organotypic hippocampal cultures. These findings reveal a possible protective mechanism by which lecanemab may slow disease progression in AD.<\/jats:p>","DOI":"10.1073\/pnas.2314450121","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T15:06:53Z","timestamp":1713193613000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["Lecanemab blocks the effects of the A\u03b2\/fibrinogen complex on blood clots and synapse toxicity in organotypic culture"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4625-9873","authenticated-orcid":false,"given":"Pradeep Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Patricia and John Rosenwald Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa 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