In this regard, impairment of insulin transport into the central nervous system, as well as abnormal expression and dysfunction of insulin receptor substrate 1 (Irs1), insulin receptor (InsR), insulin-like growth factor type 1 (IGF1), IGF1 receptor (IGFR), and insulin-degrading enzyme (IDE), were proposed to contribute to brain insulin resistance and AD development (Steen et al., 2005; Jahangir et al., 2014; Ribes-Navarro et al., 2018; Taguchi et al., 2019; Kellar and Craft, 2020). Here, IRS1 is linked to Alzheimer disease.