The effects of 12 weeks’ aerobic treadmill exercise on learning and memory ability, brain amyloid plaques, neuronal apoptosis, dendritic spine density, serum APN levels, brain APN levels, brain AdipoR1 levels, and AMPK in APP/PS1 mice, as well as the effect of autophagy-related proteins in brain cells were observed to determine the role of the APN–AdipoR1 signaling pathway in exercise’s regulation of AD autophagy abnormalities. This evidence concerns the gene ADIPOR1 and Alzheimer disease.