Our lab has recently shown that skeletal muscle-specific overexpression of Transcription Factor E-B (TFEB), a master regulator of lysosomal and mitochondrial function, mimics many of the neuroprotective benefits of exercise during aging and in the context of Alzheimer’s disease (AD) pathologies, but the effect of muscle-TFEB overexpression on AHN was unknown. The gene discussed is TFEB; the disease is early-onset autosomal dominant Alzheimer disease.