In AD, IRS2 and IRS4 interact with protein tyrosine phosphatase, non-receptor type 11 (PTPN11) and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to activate phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) which increase phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3). Here, PIK3R1 is linked to Alzheimer disease.