Therapeutic Strategies for Alzheimer's Disease in the View of Diabetes Mellitus.

Abstract

Recently, Alzheimer's disease (AD) is understood as "diabetes of the brain" or "type 3 diabetes." Recent clinical trials of anti-amyloid β-protein (Aβ) therapies have not proved to be successful. Thus, glucose-insulin metabolism in the brain is thought to be an alternative therapeutic target. Various types of antidiabetic drugs such as insulin, thiazolidinediones, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, biguanides, and others have been reported to be effective on cognitive impairment in animal models and patients with DM or AD. Here, recent reports are reviewed. While we identified apomorphine (APO) as a novel drug that promoted intracellular Aβ degradation and improved memory function in an AD mouse model, more recently, we have revealed that APO treatment improves neuronal insulin resistance and activates insulin-degrading enzyme (IDE), a major Aβ-degrading enzyme. In this context, recovery of impaired insulin signaling in AD neurons may be a promising therapeutic strategy for AD dementia.