APP and Alzheimer disease: It is well established that T2DM and metabolic syndrome (MetS) are strong risk factors for the development of AD (70–72), but this study reinforces the idea that a subtle change in glucose homeostasis, in the absence of T2DM, MetS, or hyperinsulinemia, is itself sufficient to alter APP processing, Aβ production, and AD-related pathology (12, 54, 73–76).