Further, it was definitely shown that IR/IGF1R in AD brains involve reduced receptor binding and IRS/PI3K/PKB pathway activation, as well as reduced anti-apoptosis-related mechanisms of insulin/IGF1, such as the Bcl2-associated agonist of cell death (BAD), forkhead box protein O1 (FOXO1), glycogen synthase kinase 3 beta (GSK-3B), and NFKB (for a review, see [123]). Here, INS is linked to Alzheimer disease.