APP and hyperinsulinism: Brain insulin resistance and the associated hyperinsulinemia result in Aβ accumulation [77] via several mechanisms; they increase the activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) [77], which is responsible for the proteolysis of APP into a neurotoxic form [78], and they reduce the activity of insulin-degrading enzyme (IDE), which is involved in the degradation of Aβ and the intracellular domain of APP [79].