Additionally, a reduction in insulin binding, signaling, and receptor density, particularly in the hippocampus, has been associated with aging, Alzheimer’s disease (AD), and mild cognitive impairment (Tchilian et al., 1990; Zaia and Piantanelli, 1996; Dore et al., 1997; Frolich et al., 1998; reviewed in Hoyer, 1998; Messier and Teutenberg, 2005; reviewed in Cholerton et al., 2011; Biessels and Reagan, 2015). This evidence concerns the gene INS and Alzheimer disease.