Generally, insulin resistance may contribute to AD pathogenesis through four mechanisms: dysregulation of production and clearance of Aβ, altering GSK-3β activity and promoting hyperphosphorylation of Tau, regulating microglial activation that leads to the exacerbation of neuroinflammation, and the disintegrated of tight junctions within the BBB as well as JNK-pIRS-1 pathway interruption. The gene discussed is MAPT; the disease is Alzheimer disease.