Gut dysbiosis, insulin resistance and Alzheimer’s disease: Review of a novel approach to neurodegeneration

Abstract

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) share many common features including inflammation, oxidative stress and neuronal degeneration. Insulin resistance (IR) appears to be a common path in these pathological processes. IR is an early pathogenic event in AD, which leads to augmentation of hyperphosphorylated tau and Amyloid beta (Aβ). The reviewed studies related to AD have revealed a positive association between T2DM and AD. This association was maintained in peripheral hyperinsulinemia cases without the presence of T2DM, which might be due to decreased insulin transport to the brain or the inadequate cerebral insulin production. Gut dysbiosis induces inflammation and consequently provokes both peripheral and cerebral IR and can amplify processes promoting AD. Additionally, the risk of increased progression of AD was revealed due to pre-diabetes, T2DM and gut dysbiosis. The pro-inflammatory changes might affect progression of AD pathology by inhibition of the autophago-lysosomal pathway and cerebral insulin signaling pathway. This review elaborates the role that cerebral IR might play in the underlying pathological events in AD.