How does diabetes accelerate Alzheimer disease pathology?

Abstract

Diabetes has been implicated to be a risk factor for Alzheimer disease (AD), but the underlying biological mechanisms that link the development of diabetes and AD are not fully understood. In this article, Sims-Robinson et al. summarize the mechanistic pathways that might link these two age-related diseases and discuss the possible points of intervention that future therapies could exploit to treat AD. Diabetes and Alzheimer disease (AD)—two age-related diseases—are both increasing in prevalence, and numerous studies have demonstrated that patients with diabetes have an increased risk of developing AD compared with healthy individuals. The underlying biological mechanisms that link the development of diabetes with AD are not fully understood. Abnormal protein processing, abnormalities in insulin signaling, dysregulated glucose metabolism, oxidative stress, the formation of advanced glycation end products, and the activation of inflammatory pathways are features common to both diseases. Hypercholesterolemia is another factor that has received attention, owing to its potential association with diabetes and AD. This Review summarizes the mechanistic pathways that might link diabetes and AD. An understanding of this complex interaction is necessary for the development of novel drug therapies and lifestyle guidelines aimed at the treatment and/or prevention of these diseases.