Molecular mediators of the benefits of exercise include muscle-derived myokine FNDC5/irisin that prevents neurodegeneration and rescues memory impairment in a model of Alzheimer’s disease, and liver-derived glycosylphosphatidylinositol-specific phospholipase D1 that improves cognition in aged mice44,45. The gene discussed is FNDC5; the disease is early-onset autosomal dominant Alzheimer disease.