MAPT and Alzheimer disease: Thus, mitochondria are central coordinators of energy metabolism, and concomitantly sources and targets of ROS; their structural and functional alterations by either defective insulin signaling or neurodegenerative mechanisms may represent a connecting point between T2DM and AD-associated abnormal brain insulin metabolism: on one side, Aβ accumulation and tau hyperphosphorylation synergistically alter mitochondrial bioenergetics and exacerbate oxidative stress, which accelerates neurodegenerative progression.