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Cerebral amyloid angiopathy (CAA), a major vascular contributor to cognitive decline, affects over 90% of patients with AD. This study explores the impact of tau downregulation on CAA pathogenesis.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We crossed the Familial Danish Dementia mouse model (Tg\u2010FDD), which develops vascular amyloid, with tau\u2010null (mTau\n \u2212\/\u2212<\/jats:sup>\n ) mice to generate a CAA model lacking endogenous tau (Tg\u2010FDD\/mTau\n \u2212\/\u2212<\/jats:sup>\n ). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Tau depletion ameliorated motor and synaptic impairments, reduced vascular amyloid deposition, and prevented vascular damage. Tau ablation also mitigated astrocytic reactivity and neuroinflammation associated with vascular amyloid accumulation.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n These findings provide the first in vivo evidence of the beneficial effects of tau downregulation in a CAA mouse model, supporting tau reduction as a potential therapeutic strategy for patients with parenchymal and vascular amyloid deposition.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Tau ablation improves motor function and synaptic impair, reduces cerebrovascular amyloid deposits, and prevents vascular damage in a mouse model of cerebral amyloid angiopathy (CAA).<\/jats:p>\n <\/jats:list-item>\n \n Tau reduction decreases astrocytic reactivity, alters neuroinflammatory gene expression, and enhances oligodendrocyte function, suggesting a protective role against neuroinflammation in CAA.<\/jats:p>\n <\/jats:list-item>\n \n These findings highlight tau reduction as a potential therapeutic strategy to mitigate CAA\u2010induced pathogenesis, with implications for treating patients with both parenchymal and vascular amyloid deposition.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70238","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T23:30:21Z","timestamp":1746833421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tau depletion diminishes vascular amyloid\u2010related deficits in a mouse model of cerebral amyloid angiopathy"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-3595","authenticated-orcid":false,"given":"Nur","family":"Jury\u2010Garfe","sequence":"first","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Anatomy, Cell Biology, and Physiology Indiana University 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