IRS1 and Alzheimer disease: To investigate whether AD-related activation of Ser residues on neural IRS1 emerges before or after the onset of memory decline, we employed a novel AD mouse model, APPKINL-G-F mice carrying a humanized Aβ sequence and three AD mutations, i.e., Swedish, Beyreuther/Iberian, and Arctic mutations, in the endogenous App gene [19].