{"doi":"10.3233/adr-210016","title":"Methyl-Beta-Cyclodextrin Restores K <sub>IR</sub> Channel Function in Brain Endothelium of Female Alzheimer’s Disease Mice","abstract":"Background: As the sixth-leading cause of death in the United States, Alzheimer’s disease (AD) entails deteriorating endothelial control of blood flow throughout the brain. In particular, reduced inward-rectifying K + (K IR ) channel function in animal models of aging and AD compromises endothelial function and optimal perfusion of brain parenchyma. Deficient endothelial K IR channels may result from aberrant interaction with plasma membrane cholesterol as a primary regulator of membrane fluidity and ion channels. Objective: We tested the hypothesis that mild methyl-β-cyclodextrin (MβCD) treatment to reduce membrane cholesterol may restore endothelial K IR channel function in brain endothelium of old AD mice. Methods: Membrane potential was continuously measured in isolated endothelial tubes from posterior cerebral arteries of young (1 to 3 months) and old (16 to 19 months) female 3xTg-AD mice before and after mild treatment with the cholesterol-removing agent MβCD (1 mmol/L). Elevated extracellular potassium ([K + ] E ; 15 mmol/L) and NS309 (1μmol/L) activated K IR and Ca 2+ -activated K + (SK Ca /IK Ca ) channels respectively before and after MβCD treatment. Results: SK Ca /IK Ca channel function for producing hyperpolarization remained stable regardless of age group and MβCD treatment ( ΔV m : ∼–33 mV). However, as deficient during AD, K IR channel function was restored ( ΔV m : –9±1 mV) versus pre-MβCD conditions (–5±1 mV); a progressive effect that reached –14±1 mV hyperpolarization at 60 min following MβCD washout. Conclusion: In female animals, MβCD treatment of brain endothelium selectively restores K IR versus SK Ca /IK Ca channel function during AD. Thus, the endothelial cholesterol-K IR channel interface is a novel target for ameliorating perfusion of the AD brain.","journal":"Journal of Alzheimer s Disease Reports","year":2021,"id":194160,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":763385,"name":"Erik J. Behringer","orcid":"0000-0001-6979-2796","position":1,"is_corresponding":false},{"id":659988,"name":"Md Abdul Hakim","orcid":"0000-0002-6183-7950","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:49:55.282992Z","pmid":"34755043","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":[]}