IRS1 and Alzheimer disease: Thus, in young APPKINL-G-F mice exhibiting normal memory function, the increased phosphorylation of hippocampal IRS1 at multiple Ser sites accompanied by AMPK-related low energy conditions had already occurred in the presence of increased Aβ42 level, suggesting that the elevation of Aβ42 level and/or AMPK activation provokes the activation of Ser sites on IRS1 in brains of patients with AD prior to the onset of memory decline.