Scientists reveal how exercise protects the brain from Alzheimer’s
Science Daily
February 20, 2026
AI-Generated Deep Dive Summary
Exercise has been shown to protect the brain from age-related damage linked to Alzheimer's disease by strengthening the blood-brain barrier, a critical protective system that prevents harmful substances from entering brain tissue. Researchers at UC San Francisco discovered that physical activity prompts the liver to release an enzyme called GPLD1 into the bloodstream. This enzyme targets and reduces levels of a protein named TNAP, which accumulates in cells lining the blood vessels around the brain as people age. By lowering TNAP, GPLD1 helps restore the integrity of the blood-brain barrier, reducing inflammation and preserving cognitive function.
The study highlights that as we age, the blood-brain barrier becomes increasingly permeable, allowing damaging compounds to infiltrate brain tissue and trigger inflammation associated with cognitive decline. In older mice, elevated TNAP levels were linked to memory loss and other signs of aging. However, when researchers reduced TNAP levels in aged mice, the blood-brain barrier became less leaky, inflammation decreased, and memory improved significantly. This breakthrough reveals a previously overlooked connection between physical activity, liver function, and brain health.
The findings suggest that exercise may work by triggering a body-wide response that benefits the brain indirectly. By activating the liver to produce GPLD1, which then targets TNAP in the blood vessels near the brain, exercise helps maintain the barrier's strength and resilience. This discovery opens new avenues for potential therapies aimed at reducing inflammation and preserving cognitive function in Alzheimer's patients.
The research underscores the importance of incorporating regular physical activity into our lives as we age to support brain health. The study also emphasizes that while many Alzheimer's treatments focus directly on the brain, this pathway highlights a surprising body-to-brain connection that could lead to innovative approaches to combating neurodegenerative diseases. By targeting proteins like TNAP, scientists may develop new strategies to protect the brain from damage caused by aging and inflammation.
This study is particularly significant because it identifies a mechanism that can be harnessed even in later life to mitigate cognitive decline. The researchers were able to demonstrate that reducing TNAP levels in aged mice resulted in meaningful improvements in memory and reduced inflammation, suggesting that similar approaches could be effective in humans. By better understanding the role of these proteins and enzymes in the aging process, scientists may unlock new ways to combat Alzheimer's and other age-related brain disorders.
Overall, this research not only deepens our understanding of how exercise benefits the brain but also points to
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Originally published on Science Daily on 2/20/2026