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2021 Alzheimer's Association Research Fellowship (AARF)

Exercise-Associated Modulation of Neuroinflammation in Alzheimer's Disease

What is the biology by which exercise may impact brain inflammation in Alzheimer’s?

Allison Birnbaum, Ph.D.
University of Alabama at Birmingham
Birmingham, AL - United States


The immune system is complex and serves to maintain our overall health. In our brain, the immune system specifically serves to maintain healthy nerve cells. Microglia are the primary immune cells of the brain, helping to maintain healthy nerve cells. Individuals with Alzheimer’s typically experience brain inflammation caused by dysregulation of the immune system, including increased activity of microglia, which can damage the nearby nerve cells. 

Research has shown that there is not a single cause of Alzheimer’s and dementia, but rather the disease develops over time.  Research is ongoing to understand how factors such as our environments and genetics may contribute to a person’s later life risk. 

Engaging in physical activity has been shown to benefit a person’s brain function. Recent studies show that interventions that include physical exercise may impact brain function and possibly reduce the risk of brain diseases including Alzheimer’s. However, the underlying biology that by which exercise may impact brain function and activity is not yet clear.  

Studies show that exercise releases molecules known as exerkines - that are anti-inflammatory - into the bloodstream.  One of these, FNDC5/irisin, has been found to be produced in response to physical activity and has been shown to increase metabolism, which is the efficient use of sugar and oxygen as fuel for cell activity in the body. However, little is known about the impact of FNDC5/irisin in Alzheimer’s. Dr. Allison Birnbaum believes that exercise, or mimicking the biological effects of exercise, may prevent or slow brain inflammation in Alzheimer’s.

Research Plan

Using genetically engineered Alzheimer’s-like mice, Dr. Birnbaum will investigate how the FNDC5/irisin may impact brain inflammation. These mice have also been genetically engineered to exhibit certain biology associated with exercise, including increased levels of irisin/FNDC5 and higher levels of building and turnover of proteins in muscles. Dr. Birnbaum and her colleagues will study how increased levels of irisin/FNDC5 may impact brain immune cell activation as well as brain changes including brain inflammation in the Alzheimer’s-like mice. Finally, researchers will study brain cells taken from genetically engineered Alzheimer’s-like mice in laboratory dishes, to study the impact of irisin on inflammation and other brain changes associated with Alzheimer’s.


The study results may provide insights into the impact of exercise on brain inflammation in Alzheimer’s. The results could give rise to potential therapeutic interventions to tackle Alzheimer’s and other dementia.

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