Exercise and Your Brain: What the "Muscle-Brain Axis" Means for You
By Brian Paquette, DO, MPH
The short version: When your muscles work during exercise, they send chemical signals through your bloodstream to your brain. These signals appear to protect memory and support brain health — and the best evidence available shows this benefit holds true for APOE ε4 carriers just as much as everyone else, possibly more.
How Does This Work?
Think of your muscles as a kind of pharmacy. When you exercise, they release several helpful molecules directly into your blood.
Irisin is the best-studied of these. It's made in muscle during exercise and travels to the brain, where it appears to boost a brain-growth protein called BDNF, and help brain support cells clear away amyloid-β, the sticky protein that builds up in Alzheimer's disease (Kim et al., Neuron, 2023, DOI).
Cathepsin B is another muscle-made protein. In animal studies, running raised this protein in muscle and blood, and animals that couldn't make it lost the memory benefits of exercise. In monkeys and humans, exercise raised this protein in the blood, and the amount was linked to better memory (Moon et al., Cell Metabolism, 2016, DOI). In mice bred to develop Alzheimer's-like changes, boosting this same muscle protein improved memory and coordination over six months (Pinto et al., Aging Cell, 2025, DOI).
Other muscle signals also rise after exercise, especially strength training, and are thought to support brain health as well (Ringleb et al., FASEB Journal, 2024, DOI).
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