The Role of Insulin Dysregulation in Aging and Alzheimer’s Disease

Abstract

Our knowledge of the multifaceted role of insulin in the central nervous system has expanded rapidly in recent years. It is now apparent that perturbation of this role by insulin resistance and hyperinsulinemia can increase the risk for aging-related neurodegenerative disorders such as Alzheimer's disease (AD) through a number of mechanistic pathways, delineated in elegant in vitro and animal studies. We have investigated these pathways in humans using models of insulin resistance and hyperinsulinemia. We will present results suggesting that insulin-associated effects on Ab regulation and inflammation contribute to AD pathophysiology. This premise raises the possibility that treatments aimed at improving insulin resistance will benefit patients with AD. We will review data testing this possibility in pilot therapeutic trials using insulin sensitizers and intranasal insulin.