INSR and Alzheimer disease: Specifically, both clinical and preclinical data have shown that aging and AD present with decreased central nervous system (CNS) insulin activity, lower IR expression, and reduced transport of insulin across the blood–brain barrier (Biessels, van der Heide, Kamal, Bleys, & Gispen, 2002; Cholerton, Baker, & Craft, 2011; Frazier, Ghoweri, Anderson, et al., 2019; Rhea & Banks, 2019).