How the pro-opiomelanocortin/melanocortin 4 receptor (POMC/MC4R) system works in the hippocampus, and its part in a synaptic defect in the AD, are widely unknown, although POMC-derived neuropeptides and MC4R are compromised in hippocampus-hinging synaptic plasticity. Here, POMC is linked to Alzheimer disease.