IRS1 and type 2 diabetes mellitus: Notably, T2DM animal models show elevated Tau phosphorylation and inactivation of the insulin pathway (IR and Ser-IRS-1 phosphorylation) in the brain (summarized in Mullins et al., 2017), while phospho-Ser-inhibited IRS-1 co-localized with neurofibrillary tangles (NFTs) in pyramidal neurons in the brains of AD patients (Moloney et al., 2010).