INS and Alzheimer disease: Table 3 summarizes the human studies linking IR and AD. One key mechanism involves IDE, which breaks down both insulin and Aβ in the brain [66,67]. In a neuroblastoma cell model, IR caused inactivation of IDE, which can cause the accumulation of Aβ due to the failure of Aβ clearance [68]. Additionally, IR disrupts the non-amyloidogenic pathway by reducing α-secretase expression, leading to increased Aβ peptide production [69].