Increasing evidence shows that physical activity and exercise training may delay or prevent the onset of Alzheimer’s disease (AD). In aging humans, aerobic exercise training increases gray and white matter volume, enhances blood flow, and improves memory function. The ability to measure the effects of exercise on systemic biomarkers associated with risk for AD and relating them to key metabolomic alterations may further prevention, monitoring, and treatment efforts. However, systemic biomarkers that can measure exercise effects on brain function and that link to relevant metabolic responses are lacking.