Functionally linked potassium channel activity in cerebral endothelial and smooth muscle cells is compromised in Alzheimer’s disease

Significance Patients with Alzheimer’s disease show hypoperfusion of the brain and this may contribute to disease progression. To elucidate underlying mechanisms, we studied pial arteries from 18-mo-old mice with Alzheimer’s disease due to overexpression of amyloid precursor protein. We found enhanced pressure-induced constriction of arteries because of reduction in ryanodine receptor-mediated, local calcium-release events (“Ca2+ sparks”) in arterial smooth muscle cells and a consequent decrease in the activity of large-conductance Ca2+-activated K+ (BK) channels. This phenotype was partially recapitulated by application of an amyloid-β peptide to healthy arteries. Our results will direct further research to restore cerebrovascular function, which is damaged in Alzheimer’s disease, leading to potentially new treatment options.

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