We previously reported that neurons in the hippocampal formation of patients with AD exhibited marked abnormalities in the phosphorylation states of key protein mediators of the canonical insulin signaling pathway, which involves the sequential activation of insulin receptor (IR), insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (PI3K), and alpha serine/threonine-protein kinase (AKT1) [13]. Here, IRS1 is linked to Alzheimer disease.