IRS1 and Alzheimer disease: This can be supported by the reports on age- and AD-related decrease in insulin mRNA and protein levels [11, 282, 283], IR or IGF-1R expression [11, 40, 219, 284], IRS-1 and IRS-2 levels [11], markers of Tyr kinase activity (namely, active IRS-1, PI3K, and ERK1/2) [40, 175], or a reduced association of Shc with Grb2 [30].