PSEN1 and Alzheimer disease: Importantly, in the APP/PS1 transgenic mouse model of AD, impairment of the hippocampal α-MSH/MC4R circuit exacerbates precocious synaptic dysfunctions, whereas POMC overexpression or enhancement of MC4R signaling in the hippocampus rescues the synaptic plasticity deficits21,32, indicating its role in hippocampal synaptic transmission and plasticity.