How Exercise Can Protect Against Alzheimer’s

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Exercise has well-known protective effects in Alzheimer’s disease (AD).

In a study that appeared in Nature Neuroscience, a research team looked for exercise-induced changes in gene activity in a mouse model of AD. They focused on a region of the hippocampus called the dentate gyrus. The hippocampus is essential for memory and learning, and the dentate gyrus is where new hippocampal neurons form. This region is also susceptible to changes during both exercise and AD.

For exercise, mice were allowed to run freely on a wheel over a 60-day period. The AD mice who exercised had better cognitive function than the sedentary AD group. Exercise led to changes in gene activity in both healthy mice and AD mice, but the affected genes differed between the groups.

Certain gene activity changes were specific to AD mice across various cell types. Exercise restored some of these genes’ activities to healthy levels. Many of these recovered genes occurred in immature neurons, suggesting exercise has an impact on new neuron formation in the hippocampus. One exercise-recovered gene, Atpif1, was particularly important for neuron development and survival.

Exercise also had positive effects on gene activity in several types of brain support cells: Oligodendrocyte progenitor cells, which produce the cells that make the insulating myelin sheath on neurons; a subset of immune microglia that activate in response to AD and can reduce the damage it causes; and astrocytes, which help maintain the brain-blood barrier.

Finally, the team compared their mouse data with human AD and control brain tissue data. Many of the genes with abnormal activity in the mouse AD model were similarly affected in people with a hereditary form of AD. This suggests the findings in the mouse model may be applicable to AD in humans.

More exercise is associated with lower risk of AD, better cognitive function and less cognitive decline in people with AD. The cellular level effects of exercise remain unclear but could reveal novel ways to treat AD and other neurodegenerative diseases. —Brian Doctrow, NIH Research Matters