2024 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Uncovering the Role of an African-specific ABCA7 Frameshift Deletion on Lipid Metabolism and Alzheimer’s Disease

What are the genetic factors that contribute to increased Alzheimer’s risk in individuals of African ancestry?

Nam Younji, Ph.D.
University of Miami
Miami, FL - United States

Background

According to the 2024 Alzheimer’s Association Facts and Figures report, Black Americans are nearly two times more likely to develop Alzheimer’s than White Americans. Researchers are exploring the potential environmental and genetic factors that contribute to this disparity. Several studies have identified a gene, called ABCA7, that plays a role in the production of the beta-amyloid protein and may increase one’s risk of developing Alzheimer’s (beta-amyloid protein accumulates in the form of amyloid plaques in Alzheimer’s - one of the hallmark brain changes of the disease). Additionally, ABCA7 can interact with another gene that plays a role in Alzheimer’s risk, called APOE, to transport lipids (fats) in the brain. 

In preliminary studies, Dr. Nam Youji and colleagues have identified a genetic variant of ABCA7 that is associated with Alzheimer’s risk in individuals of African ancestry. However, the mechanisms linking this variant and Alzheimer’s risk are unknown.

Research Plan

For their studies, Dr. Youji and the team will use a specialized type of stem cell collected from adult human tissue called iPSCs (induced Pluripotent Stem Cells), which can be programmed to grow into any type of cell in the body, including brain cells. They will use iPSCs collected from individuals of African ancestry who do or do not have the ABCA7 variant and measure how the ABCA7 variant impacts lipids and accumulation of amyloid plaques and tau tangles (another hallmark brain change observed in Alzheimer’s). Next, the researchers will study how the ABCA7 variant and the genetic variations of APOE, including APOE-e2, APOE-e3 and APOE-e4, interact and alter breakdown of lipids into energy in iPSCs.

Impact

Results of this study may provide insights into the role of ABCA7 in Alzheimer’s risk. If successful, the findings could lay the foundation to develop new therapeutic strategies to treat or prevent Alzheimer’s in individuals of African ancestry who are at greater risk of developing the disease.