{"doi":"10.1002/alz.70238","title":"Tau depletion diminishes vascular amyloid‐related deficits in a mouse model of cerebral amyloid angiopathy","abstract":"INTRODUCTION: Tau is essential for amyloid beta (Aβ)-induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. 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. METHODS: ). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed. RESULTS: 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. CONCLUSION: 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. HIGHLIGHTS: 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). Tau reduction decreases astrocytic reactivity, alters neuroinflammatory gene expression, and enhances oligodendrocyte function, suggesting a protective role against neuroinflammation in CAA. These findings highlight tau reduction as a potential therapeutic strategy to mitigate CAA-induced pathogenesis, with implications for treating patients with both parenchymal and vascular amyloid deposition.","journal":"Alzheimer s & Dementia","year":2025,"id":523318,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.922,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1223801,"name":"Enrique Chimal‐Juárez","orcid":"0000-0002-1820-1068","position":1,"is_corresponding":false},{"id":648402,"name":"Henika Patel","orcid":"0000-0002-2654-4669","position":2,"is_corresponding":false},{"id":970926,"name":"Jonathan Martínez-Pinto","orcid":"0000-0001-8628-892X","position":3,"is_corresponding":false},{"id":1396258,"name":"Kathryn Vanderbosch","orcid":null,"position":4,"is_corresponding":false},{"id":908898,"name":"Muriel D. Mardones","orcid":"0000-0002-6782-2776","position":5,"is_corresponding":false},{"id":648404,"name":"Abigail Perkins","orcid":"0000-0001-7562-1635","position":6,"is_corresponding":false},{"id":285571,"name":"Gonzalo Viana Di Prisco","orcid":"0000-0002-6138-0057","position":7,"is_corresponding":false},{"id":272871,"name":"Yamil Marambio","orcid":null,"position":8,"is_corresponding":false},{"id":271115,"name":"Rubén Vidal","orcid":"0000-0002-5803-3871","position":9,"is_corresponding":false},{"id":285573,"name":"Brady K. Atwood","orcid":"0000-0002-7441-2724","position":10,"is_corresponding":false},{"id":271116,"name":"Cristian A. Lasagna‐Reeves","orcid":"0000-0002-5499-3082","position":11,"is_corresponding":false},{"id":648405,"name":"Nur Jury","orcid":"0000-0002-1143-3595","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40346706","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}