Insulin Resistance and Alzheimer’s Disease

Abstract

Alzheimer disease (AD) is known as a form of type III diabetes due to its similar cellular responses and pathogenesis. Insulin alters normal brain function and peripheral glucose metabolism, and conditions that are related to insulin dysregulation, such as obesity, diabetes mellitus, and cardiovascular disease, have potentially harmful effects on brain function. Many reports have demonstrated that insulin resistance increases age-related memory impairments and is a risk factor for AD. The molecular and cellular link between insulin resistance and AD, however, is unknown. We discuss the potential mechanisms of these metabolic disorders in the pathogenesis of AD. Glucose homeostasis is critical for energy maintenance, neurogenesis, neuronal survival, and synaptic plasticity, which are required for learning and memory. During insulin resistance, one develops reduced sensitivity to insulin, resulting in hyperinsulinemia, and this impairment in insulin signaling mediates the pathogenesis of AD, which manifests as brain inflammation, oxidative stress, alterations in amyloid beta (A┚) levels, and cell death. Human and experimental animal studies have noted that drugs that modulate insulin resistance decrease the accumulation of A┚ in the brain and the cognitive impairments that are associated with AD. Therapeutic strategies that target the link between insulin resistance and AD might benefit the development of future AD drugs.