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2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Studies of MOAG-4/SERF-2 as a link between obesity and Alzheimer's disease

Can the build-up of proteins be the link between obesity and Alzheimer’s risk?

Eyleen O'Rourke, Ph.D.
University of Virginia
Charlottesville, VA - United States



Background

As obesity prevalence increases worldwide, there are also increases in the consequences for overall health related to obesity. Obesity is associated with increased risk of type 2 diabetes, high blood pressure, and vascular (blood vessel) disorders which impact multiple systems in the body, including the brain. This in turn may increase the risk of developing Alzheimer’s in older adults. However, the mechanisms linking obesity and Alzheimer’s risk are unclear.
 
In preliminary findings, Dr. Eyleen O’Rourke and colleagues have demonstrated that there may be a link between obesity and a build-up of proteins in the brain, which could contribute to an individual’s risk of developing Alzheimer’s.

Research Plan

Building on their initial findings, Dr. O’Rourke and the team will examine how obesity changes a specific protein called MOAG4 (also known as SEF2) which may play a role in the build-up of proteins commonly observed in Alzheimer’s brains. To do this, they will utilize an animal model called Caenorhabditis elegans, a species of roundworm that develops similar Alzheimer’s-related brain changes and cognitive impairment as humans. They will feed the roundworms that either do or do not have MOAG4 a high-fat diet and examine how levels of MOAG4 impact genes that are linked to obesity and Alzheimer’s. Next, the researchers will measure cognitive function in the same roundworms to examine the relationship between MOAG4 and cognition. Lastly, the team will use their findings in roundworms to create a genetically engineered Alzheimer’s-like mouse model to confirm their findings in another species.

Impact

The results of this project may help us better understand the links between obesity and Alzheimer’s risk. If successful, the findings could also lead to new interventions or therapies to reduce Alzheimer’s risk in this population.

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