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2019 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Targeting FNDC5/irisin to improve brain metabolism in Alzheimer’s disease

How does a hormone produced during physical activity protect nerve cell function in the brain?
 

Mychael Lourenco, Ph.D.
Universidade Federal do Rio de Janeiro
Rio de Janeiro, Brazil



Background

Engaging in physical activity has been shown to improve brain function. Recent studies show that lifestyle interventions that include physical exercise may promote brain health and possibly reduce risk of brain diseases like Alzheimer’s.  Studies have found that a hormone called FNDC5/irisin is produced in response to physical activity and increases cell metabolism, which is the efficient use of sugar and oxygen as fuel for cell activity in the body. Far less is known about the role of FNDC/irisin levels within the brain, which Dr. Mychael Lourenco is proposing to explore in this study. In preliminary studies, Dr. Lourenco has found that FNDC5/irisin levels are low in the brains of people with Alzheimer’s disease and genetically engineered Alzheimer’s-like mice.
 

Research Plan

Dr. Lourenco will test whether increasing the levels of FNDC5/irisin, will restore nerve cell metabolism in genetically engineered Alzheimer’s-like mice. The researchers will also test the impact of FNDC5/irisin levels in the accumulation of the protein fragments such as beta-amyloid and tau protein in the brain, which form plaques and tau tangles respectively, the two major hallmarks of Alzheimer’s disease. Furthermore, Dr. Lourenco will use brain scans to track the uptake of sugar throughout the brain to check if FNDC5/irisin impacts abnormal metabolism of sugar by nerve cells and their networks.
 

Impact

This project will help shed light on how physical activity benefits brain health and may reduce risk or slow onset of Alzheimer’s. If successful, the study results may also lead to the development of therapies that improve nerve cell metabolism in the brain to support memory function in people with Alzheimer’s disease.
 

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