{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:09Z","timestamp":1792790349561,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,11]]},"group-title":"Neuroscience","reference-count":19,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute on Aging","award":["R01AG054598-06"],"award-info":[{"award-number":["R01AG054598-06"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute on Aging","award":["K99AG088296"],"award-info":[{"award-number":["K99AG088296"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["K08NS131530"],"award-info":[{"award-number":["K08NS131530"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Alzheimer's Association","award":["23AARF-1028885"],"award-info":[{"award-number":["23AARF-1028885"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Anti-amyloid-\u03b2 (A\u03b2) immunotherapy improves cognitive outcomes in Alzheimer\u2019s disease (AD) but is associated with amyloid-related imaging abnormalities (ARIA), through poorly understood mechanisms. To define how anti-A\u03b2 antibodies acutely engage brain immune and vascular compartments, we developed a longitudinal in vivo two-photon imaging platform to track microglial dynamics, peripheral immune cell recruitment, and vascular responses in APP\/PS1 mice. Anti-A\u03b2 antibodies, including aducanumab and lecanemab, rapidly initiated microglial activation and spatial reorganization within 24 hours of dosing, with recruitment to plaque-associated regions, stabilizing plaque growth. Aducanumab and lecanemab also triggered a rapid and transient cerebrovascular immune response characterized by rolling and adhesion of peripheral immune cells along leptomeningeal vessels, accompanied by endothelial activation. Immune cell characterization revealed recruitment of innate immune cells (Iba1\u207aKi67\u207a monocytes and Ly6G\u207a neutrophils) and proliferative CD3\u207a T cells into the vascular compartment following treatment. Prophylactic treatment with high-dose dexamethasone reduced the number of adherent cells without affecting microglial activation. Depletion of brain-resident immune cells similarly reduced peripheral immune cell recruitment, supporting their contribution to leukocyte recruitment. Postmortem brain tissue from an AD patient treated with lecanemab showed higher proliferation-associated monocyte signature scores, suggesting translational relevance to the proliferative myeloid response observed in our mouse models. These findings demonstrate that anti-A\u03b2 immunotherapy rapidly initiates a coordinated central and peripheral immune response at the leptomeningeal interface. These early immune\u2013vascular interactions represent a plausible initiating mechanism for ARIA and provide a mechanistic framework to guide strategies for mitigating ARIA risk.<\/jats:p>","DOI":"10.64898\/2026.09.07.749938","type":"posted-content","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:55:12Z","timestamp":1789167312000},"source":"Crossref","is-referenced-by-count":0,"title":["Brain-resident myeloid cells promote rapid leukocyte adhesion in leptomeningeal vessels after anti-A\u03b2 immunotherapy"],"prefix":"10.64898","author":[{"given":"Moustafa","family":"Algamal","sequence":"first","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadzanai","family":"Ndambakuwa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarena","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Sanchez-Mico","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Gillani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryan","family":"Rajput","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshita","family":"Palanivelu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy R.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kivilcim","family":"Kilic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"El Khoury","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saef","family":"Izzy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariel G.","family":"Kozberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Bacskai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mass General Brigham, Harvard Medical School, Charlestown, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091606301151000_2026.09.07.749938v1.1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41582-024-01053-8","article-title":"Amyloid-related imaging abnormalities: manifestations, metrics and mechanisms","volume":"21","year":"2025","journal-title":"Nat. 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