Communication breakdown: Impaired pericyte KATP channels in a model of Alzheimer’s disease

The brain requires a continuous supply of blood in proportion to its metabolic activity, a process that is disrupted in Alzheimer’s disease. However, the mechanisms responsible for altered brain blood flow regulation in Alzheimer’s disease remain poorly defined. In an earlier issue of JGP, Hariharan et al. (https://doi.org/10.1085/jgp.202614014) significantly add to our understanding of this pathology by showing that ATP-Sensitive K+ (KATP) channels in thin strand pericytes on cerebral capillaries are compromised at 6–8 weeks in the 5X-FAD mouse model of Alzheimer’s disease. They also confirmed that cerebral capillary endothelial inward rectifier K+ (KIR) channels are crippled and importantly show that this defect occurs at 2–4 months, before significant cognitive defects have been reported. Combined, these channelopathies severely attenuate electrical communication along cerebral capillaries, dampening blood flow regulation. These novel findings present new therapeutic targets to slow or possibly prevent the reduced cerebral blood flow in Alzheimer’s disease, perhaps delaying or preventing cognitive decline. Like all scientific advances, they also open the door for new areas of research.