Reduced sensitivity to insulin and IGF signals in AD are observed across multiple levels of cell signal response, including reduced insulin receptor (IR) sensitivity, inhibition of secondary messengers (i.e., IR substrate-1), and decreased IR and IGF receptor (IGFR) expression (Watson and Craft, 2003; Rivera et al., 2005; Steen et al., 2005; Holscher and Li, 2010; de la Monte, 2012; Talbot et al., 2012; Freiherr et al., 2013; Stanley et al., 2016). This evidence concerns the gene INS and Alzheimer disease.