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2016 Grants - Ojelade
Understanding CD2AP's Role in Alzheimer's Disease
Shamsideen Adeniyi Ojelade, Ph.D.
Baylor College of Medicine
2016 Alzheimer’s Association Research Fellowship to Promote Diversity (AARF-D)
How do variations in the CD2AP gene affect nerve cell function and the risk for Alzheimer’s disease?
An important focus of Alzheimer’s research is discovering the genetic factors that may increase an individual’s risk for developing the disease. Recent studies conducting large scans of the human genome called “genome-wide association studies” (GWAS) have identified variations in the gene for CD2-associated protein (CD2AP) that may be associated with increased Alzheimer’s risk. The CD2AP gene produces proteins that are known to be important for kidney function, but its role in the brain is not yet clear.
In initial studies, Shamsideen Adeniyi Ojelade, Ph.D., and colleagues used fruit flies to examine CD2AP in the brain and found that it may relate to the function of synapses, the structures through which nerve cells communicate with each other. The researchers also found that fruit flies that lack the CD2AP gene were more vulnerable to the effects of abnormal tau protein. Abnormal tau is known to accumulate into tangles in the brain during Alzheimer’s disease. These lines of evidence suggest that CD2AP may play a role in brain health, but more research is needed to better understand the underlying mechanisms involved.
Dr. Ojelade and colleagues will conduct a larger study in fruit flies to examine the various proteins that are impacted by changes in the CD2AP gene and how this relates to synapse function. Fruit flies offer scientists a method to study complex genetic interactions that would be difficult or time consuming in mice or people. Once the researchers narrow down which changes seem most relevant, they will validate these findings in mice genetically-engineered to lack the CD2AP gene. They will measure changes in synaptic activity, nerve cell function and brain levels of abnormal tau as the animals age.
The results of this study could improve our understanding of the role of CD2AP in the brain and help reveal how alterations in this gene may promote the risk for Alzheimer’s disease. Most importantly, this work may reveal novel genetic targets for the future development of treatments to prevent, slow or treat Alzheimer’s disease.