Insulin resistance: a connecting link between Alzheimer's disease and metabolic disorder

Recent evidence suggests that Alzheimer's disease (AD) is closely linked with insulin resistance, as seen in type 2 diabetes mellitus (T2DM). Insulin signaling is impaired in AD brains due to insulin resistance, ultimately resulting in the formation of neurofibrillary tangles (NFTs). AD and T2DM are connected at molecular, clinical, and epidemiological levels making it imperative to understand the contribution of T2DM, and other metabolic disorders, to AD pathogenesis. In this review, we have discussed various modalities involved in the pathogenesis of these two diseases and explained the contributing parameters. Insulin is vital for maintaining glucose homeostasis and it plays an important role in regulating inflammation. Here, we have discussed the roles of various contributing factors like miRNA, leptin hormone, neuroinflammation, metabolic dysfunction, and gangliosides in insulin impairment both in AD and T2DM. Understanding these mechanisms will be a big step forward for making molecular therapies that may help maintain or prevent both AD and T2DM, thus reducing the burden of both these diseases.