Tau Loss of Function, by Deletion or Aggregation, Contributes to Peripheral Insulin Resistance

Epidemiological association between Alzheimer’s disease (AD) and type 2 diabetes is a critical health concern that has not been resolved yet at the molecular mechanistic level. While brains of AD patients and AD transgenic mouse models display impaired insulin signaling, there is no clear understanding of the role of peripheral insulin resistance in the pathogenesis of AD. Moreover, alterations in key insulin signaling proteins have been also implicated in AD, among which GSK‐3β, is also one of the important kinases for the phosphorylation of the microtubule‐associated protein tau (tau), one of the pathological hallmarks of AD. The goal of this study is to determine the role of systemic insulin resistance in the pathophysiology of AD by testing the hypothesis that functional tau is important for peripheral insulin sensitivity, and its deletion or loss‐of‐function promotes peripheral insulin resistance.