Further, impairments in insulin signaling downstream machinery have been reported in post-mortem brain tissue and in animal models of AD (Steen et al., 2005; Lester-Coll et al., 2006; de la Monte, 2009; Moloney et al., 2010; Bomfim et al., 2012; Craft, 2012; Talbot et al., 2012; Lourenco et al., 2013; Clarke et al., 2015). This evidence concerns the gene INS and Alzheimer disease.