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We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-\u03b2 protein (anti-A\u03b2) using asymmetrical Fc mutations (ATV\n                    <jats:sup>cisLALA<\/jats:sup>\n                    ) that mitigates TfR-related liabilities and retains effector function when bound to A\u03b2. Administration of ATV\n                    <jats:sup>cisLALA<\/jats:sup>\n                    :A\u03b2 in mice exhibited broad brain distribution and enhanced parenchymal plaque target engagement. This biodistribution reduced ARIA-like lesions and vascular inflammation. Taken together, ATV\n                    <jats:sup>cisLALA<\/jats:sup>\n                    has the potential to improve the next generation of A\u03b2 immunotherapy through enhanced biodistribution mediated by transport across the blood-brain barrier.\n                  <\/jats:p>","DOI":"10.1126\/science.ads3204","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T18:00:31Z","timestamp":1754589631000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":66,"title":["Transferrin receptor\u2013targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA"],"prefix":"10.1126","volume":"389","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-5996","authenticated-orcid":true,"given":"Michelle E.","family":"Pizzo","sequence":"first","affiliation":[{"name":"Denali Therapeutics, Inc., South San Francisco, CA, 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