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2021 Alzheimer's Association Research Grant (AARG)

Investigating African American-specific ABCA7 variants using hiPSCs

What factors may impact the risk of developing Alzheimer’s among blacks/African Americans?

David Brafman, Ph.D.
Arizona State University
Tempe, AZ - United States


According to the 2021 Alzheimer’s Association Facts and Figures report, older blacks/African Americans are twice as likely to have Alzheimer’s or other dementia than older whites. Researchers are studying the reasons for this disparity.  Researchers are focusing on identifying genetic factors that may impact a person’s the risk for developing Alzheimer’s. Several studies have identified a gene called ABCA7 that may increase the risk of Alzheimer’s. This gene provides instructions for a protein involved in the production of beta-amyloid that can accumulate into plaques, a hallmark brain change observed in Alzheimer’s. Studies have identified variations of ABCA7 largely found among blacks/African Americans. Researchers are trying to understand how these variations could impact a person’s risk for developing Alzheimer’s.

Dr. David Brafman and colleagues have developed a genetic engineering method called TREE (transient reporter for editing enrichment) to introduce different versions of the ABCA7 gene into cells to study their function in detail.

Research Plan

Dr. Brafman’s team will use a specialized type of stem cell collected from adult human tissue called iPSCs (induced Pluripotent Stem Cells). This will be collected from cognitively unimpaired individuals and those with Alzheimer’s. iPSCs can be programmed to grow into any type of cell in the body, including brain cells. Using these cells, the researcher will develop a three-dimensional brain-like structure that may better enable researchers to explore how brain changes observed in Alzheimer’s may impact individual brain cells as well as the interactions between cells. Using the TREE technique, the researchers will introduce different genetic variations of ABCA7 into nerve cells of the brain-like structure. 

The researchers will then investigate the impact of the genetic variations of ABCA7 on the nerve cells with multiple approaches- Dr. Brafman’s team will study how variations in the ABCA7 may impact instructions for the protein involved in the production of beta-amyloid.  In another approach, the researchers will study how the genetic variations of ABCA7 may impact which of the genes associated with nerve cell health and function may be turned on or off. Dr. Brafman believes that these experiments may help us understand the biology by which genetic variations of ABCA7 may impact brain changes observed in Alzheimer’s. 


The study results may help provide insights into how genetic risk factors may be associated with health disparities in Alzheimer’s and dementia among underrepresented populations. If successful, the results could give rise to potential therapeutic targets to tackle Alzheimer’s in blacks/African Americans.

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