Figure 1.

The role of AdipoQ deficiency in the pathogenesis of Alzheimer’s disease through AMPK inactivation. In neurons, AdipoQ deficiency leads to decreased AMPK activation and increased phosphorylation of IRS-1^S616 that inhibits the pIRS-1^Tyr formation, and thus deactivates insulin signaling. On the other hand, insulin resistance is gradually developed and reduces pAkt^S473 Levels. Thus, decreased Akt induction and increased GSK3β activation results in increased Aβ production and tau phosphorylation. Furthermore, insulin resistance exacerbates the extracellular Aβ deposition as well as impaired synaptic plasticity. AMPK, AMP-activated protein kinase; IRS, insulin receptor substrate; GSK3β, glycogen synthase kinase 3β; Akt, protein kinase B; Aβ, amyloid beta peptide.