However, peripheral FNDC5/irisin overexpression rescued memory impairment in APP/PS1 ΔE9 mice, whereas peripheral or cerebral FNDC5/irisin blockade attenuated the neuroprotective actions of physical exercise on synaptic plasticity and memory, making FNDC5/irisin a novel agent capable of opposing synaptic failure and memory impairment in AD [15]. Here, FNDC5 is linked to Alzheimer disease.