Scientists Identify How Exercise May Help Protect the Brain From Alzheimer's

A new study suggests that exercise may help protect the brain from Alzheimer's Disease by strengthening the Blood-Brain Barrier, a critical structure that shields the brain from harmful substances circulating in the bloodstream. The research, conducted by scientists at the University of California, San Francisco, was published in the journal Cell.

Previous studies had shown that physical activity increases levels of a protein called Glycosyl-phosphatidylinositol-Specific Phospholipase D1 (GPLD1) in the blood. This protein is associated with improved brain health and reduced cognitive decline. In the new study, researchers discovered how GPLD1 helps protect the brain by regulating another molecule called Tissue-Nonspecific Alkaline Phosphatase (TNAP).

TNAP normally helps maintain the permeability of the blood-brain barrier during stressful conditions. However, with aging, TNAP can accumulate in the cells of the barrier and impair its function. The researchers found that GPLD1 helps remove or “prune” excess TNAP from these cells, thereby strengthening the barrier and reducing inflammation in the brain.

Experiments in mice supported this mechanism. Young mice engineered to have higher TNAP levels in their blood-brain barrier developed cognitive decline similar to older animals. Conversely, older mice engineered to have lower TNAP levels showed fewer leaks in the barrier, reduced inflammation, and improved cognitive performance.

In mouse models of Alzheimer’s disease, increasing GPLD1 levels or reducing TNAP was also associated with fewer deposits of Amyloid Beta, a hallmark protein linked to Alzheimer’s pathology.

Although the study was conducted in mice, the findings suggest that exercise-triggered biological processes may help protect the aging brain. Researchers hope that understanding this mechanism could eventually lead to therapies that mimic the brain-protective effects of exercise, especially for individuals who are unable to engage in regular physical activity.

REFERENCE: Bieri, Gregor et al.; Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature; Cell, Volume 189; DOI: 10.1016/j.cell.2026.01.024