Indeed, obesity and peripheral hyperglycemia, by promoting insulin resistance and hypoglycemia at brain level, lead to decreased O-GlcNAcylation of APP and Tau and to increased production of toxic Aβ amyloid and Tau aggregates, which are hallmarks of AD [27,28,29,30,31]. Here, MAPT is linked to obesity due to melanocortin 4 receptor deficiency.