LEP and Alzheimer disease: In this way, the disruption of leptin signaling in a mouse model of AD reduces Akt in parallel with the upregulation of the suppressor of cytokine signaling 3 (SOCS3) in the hippocampus [43], and we have demonstrated that the central infusion of leptin reduced the association of SOCS3 with IGF-IR, increasing its phosphorylation and activation of downstream targets [44].