Brain insulin signaling-related molecules, such as IGF-IR and InsR, are upstream mediators of neuroprotective PI3K/Akt/GSK-3β signaling and are dysregulated in the AD brain (Bondy and Cheng, 2004; Lee et al., 2005; Messier and Teutenberg, 2005; Moloney et al., 2010). This evidence concerns the gene INS and Alzheimer disease.