Prediabetes and Alzheimer's Disease

Abstract

Aging patients with diabetes are at higher risk of developing Alzheimer's disease. Emerging evidences demonstrate the role of brain insulin resistance, which is a key mediator in prediabetes and diabetes mellitus that may lead to Alzheimer's disease. Insulin and insulin-like growth factors regulate many biological processes such as axonal growth, protein synthesis, cell growth, gene expression, proliferation, differentiation, and development. Among these, the energy metabolism and synaptic plasticity are the major transduction processes regulated by insulin, which are the core objectives for learning and memory. It was also proposed that hyper insulinemia induced insulin resistance results in injury to the central nervous system by the activation of glycogen synthase kinase 3β which is the key ailment in the cognitive decline. Hence, the endogenous brain specific insulin impairments and signaling account for the majority of Alzheimer's abnormalities.

Keywords: Aging; Alzheimer's disease; glycogen synthase kinase 3β; insulin resistance; prediabetes.

Fig. 1

Insulin-mediated signal transduction leading to the pathogenesis of AD via GSK. IRS is insulin receptor substrate, PI3 Kinase is phosphoinsotide 3 kinase, PIP3 is phosphatidyl inositol (3,4,5)-triphosphate, Akt is protein kinase B, and GSK3β is glycogen synthase kinase 3 beta.

Fig. 2

Link between insulin defects and the formation of major pathological hallmarks in AD. GSK3α is glycogen synthase kinase 3 alpha and GSK3β is glycogen synthase kinase 3 beta.