- Scientists have identified a mechanism in mice that helps explain how exercise supports brain health as we age.
- Physical activity boosted a liver enzyme that improved the blood-brain barrier and reduced brain inflammation, with better memory performance in older mice.
- It is early-stage science, but it points to a fresh therapeutic angle: protecting the brain by targeting blood vessels and barrier function.
Your brain is protected by a tightly regulated barrier made from specialised blood vessels and supporting cells.
It controls what gets in and what stays out. With ageing, this barrier can become leaky, allowing inflammatory signals and harmful molecules to reach brain tissue more easily.
Inflammation is strongly linked with cognitive decline and is seen in Alzheimer’s disease. So anything that protects the blood-brain barrier is an interesting target.
What the research discovered
Earlier work showed exercising mice produced higher levels of an enzyme called GPLD1 in the liver.
GPLD1 itself does not cross into the brain, which raised a key question: how can it improve cognition if it cannot enter the brain?
The new work suggests GPLD1 acts on the vasculature around the brain by trimming a protein called TNAP from the surface of blood-brain barrier cells.
TNAP builds up with age and appears to weaken barrier integrity. Lower TNAP meant a less permeable barrier, less inflammation, and improved memory measures in older mice.
Why TNAP is the “proof” step, not just a correlation
The team tested causality by manipulating TNAP itself. Increasing TNAP in young mice produced cognitive problems that looked more like ageing.
Reducing TNAP in older mice improved barrier function and memory performance. That makes TNAP look like a driver, not just a bystander.
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What this means for people with diabetes
Type 2 diabetes is associated with higher dementia risk, partly through vascular damage, inflammation, and metabolic stress.
This study reinforces a practical message: exercise is not just for weight and glucose. It may protect the brain through whole-body pathways that include the liver and blood vessels.
It does not mean you need heroic workouts.
The most brain-protective exercise is the one you actually maintain for years.
