{"doi":"10.1002/alz.14438","title":"Sex‐specific mechanisms of cerebral microvascular BK <sub>Ca</sub> dysfunction in a mouse model of Alzheimer's disease","abstract":"Abstract INTRODUCTION Cerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca 2+ ‐activated K + channels (BK Ca ) regulate cerebrovascular reactivity and are impaired in AD. BK Ca activity depends on intracellular Ca 2+ (Ca 2+ sparks) and nitro‐oxidative post‐translational modifications. However, whether these mechanisms underlie BK Ca impairment in AD remains unknown. METHODS Cerebral arteries from 5x‐FAD and wild‐type (WT) littermates were used for molecular biology, electrophysiology, ex vivo, and in vivo experiments. RESULTS Arterial BK Ca activity is reduced in 5x‐FAD via sex‐dependent mechanisms: in males, there is lower BK α subunit expression and less Ca 2+ sparks. In females, we observed reversible nitro‐oxidative modification of BK Ca . Further, BK Ca is involved in hemodynamic regulation in WT mice, and its dysfunction is associated with vascular deficits in 5x‐FAD . DISCUSSION Our data highlight the central role played by BK Ca in cerebral hemodynamic regulation and that molecular mechanisms of its impairment diverge based on sex in 5x‐FAD . Highlights Cerebral microvascular BK Ca dysfunction occurs in both female and male 5x‐FAD . Reduction in BK α subunit protein and Ca 2+ sparks drive the dysfunction in males. Nitro‐oxidative stress is present in females, but not males, 5x‐FAD . Reversible nitro‐oxidation of BK α underlies BK Ca dysfunction in female 5x‐FAD .","journal":"Alzheimer s & Dementia","year":2024,"id":460609,"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":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1288763,"name":"Felipe D. Polk","orcid":"0000-0001-7890-4737","position":1,"is_corresponding":false},{"id":1289228,"name":"Paige E. Martin","orcid":null,"position":2,"is_corresponding":false},{"id":1289229,"name":"Stephenie H. Thai","orcid":null,"position":3,"is_corresponding":false},{"id":1289230,"name":"Andrea Savu","orcid":null,"position":4,"is_corresponding":false},{"id":1289231,"name":"Matthew Gonzales","orcid":null,"position":5,"is_corresponding":false},{"id":1289232,"name":"Allison Kath","orcid":null,"position":6,"is_corresponding":false},{"id":459894,"name":"Michael T. Gee","orcid":"0000-0002-6594-653X","position":7,"is_corresponding":false},{"id":969171,"name":"Paulo W. Pires","orcid":"0000-0001-5972-4554","position":8,"is_corresponding":false},{"id":1288762,"name":"Josiane F. Silva","orcid":"0000-0002-6623-7946","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:04:07.925246Z","pmid":"39698895","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":[]}