IRS1 and Alzheimer disease: Mechanisms such as hyperphosphorylation of insulin receptor substrate-1 (IRS-1), oxidative stress, chronic neuroinflammation, and amyloid-β/tau-mediated toxicity have been implicated in impairing insulin signaling in the AD brain (Boura-Halfon and Zick, 2009; Rains and Jain, 2011; Copps and White, 2012; El Khoury et al., 2014; Cheignon et al., 2018; Gali et al., 2019; Gonçalves et al., 2019; Zheng and Wang, 2021).