Neuronal insulin resistance instigated by hyperphosphorylation of IRS-1 at the Ser636/312/307 residues and downregulation of p-IRS-1Tyr 632 has been associated with AD pathology and reported in Aβ and APP/PS1 mouse AD models as well as HFD and Adipo−/− mice [8, 9, 14–16, 21, 48]. The gene discussed is APP; the disease is Alzheimer disease.