Alpha-endosulfine has the sulfonylurea-like ability to block ATP-sensitive potassium (K(ATP)) channels, which can stimulate insulin secretion in beta cell. Although the blockade of K(ATP) channels has been reported to be involved in neurotransmitter release, the neurobiological role of alpha-endosulfine has not been studied yet. We examined the protein levels of alpha-endosulfine in frontal cortex and cerebellum from patients with Alzheimer's disease (AD). Alpha-endosulfine was extremely decreased in both regions of AD compared to controls. This could result in the continuous opening of K(ATP) channels with subsequent decrease of neurotransmitter release and change of potassium fluxes. This study is of great significance for providing a neurobiological function of brain alpha-endosulfine and furthermore, alpha-endosulfine could serve as a useful marker for the diagnosis of AD and a target for drug treatment.