A key Alzheimer’s gene emerges in African American brain study
Scientists studying Alzheimer’s in African Americans have uncovered a striking genetic clue that may cut across racial lines. In brain tissue from more than 200 donors, the gene ADAMTS2 was significantly more active in people with Alzheimer’s than in those without it. Even more surprising, this same gene topped the list in an independent study of White individuals. The discovery hints at a common biological pathway behind Alzheimer’s and opens the door to new treatment strategies.
Alzheimer disease (AD) affects African Americans (AA) at roughly twice the rate seen in White or European-ancestry (EA) individuals living in the U.S. Researchers attribute part of this disparity to social and structural factors, including unequal access to health care, differences in educational opportunities, and known biases in cognitive testing. African Americans also have higher rates of health conditions such as cardiovascular disease and diabetes, both of which increase the risk of developing AD.
Many previous studies have examined gene expression (measure of the amount of protein encoded by a gene) in brain tissue from people with Alzheimer's compared with those without the disease. However, most of this research focused on EA or mixed-ancestry groups. In many cases, the number of AA participants was either not reported or too small to allow meaningful conclusions about genetic patterns specific to this population.
Largest Brain Study Identifies New Alzheimer's Genes
In the largest Alzheimer's study to date using brain tissue from African American donors, scientists at Boston University Chobanian & Avedisian School of Medicine identified numerous genes that behaved differently in people with AD compared with individuals without the disease. Many of these genes had not been previously linked to Alzheimer's by other genetic studies.
The strongest signal came from the ADAMTS2 gene. Researchers found that its activity level was 1.5 fold higher in brain tissue from individuals with autopsy-confirmed AD than in tissue from controls.
Consistent Findings Across Independent Studies
The research team analyzed gene expression data from post-mortem prefrontal cortex tissue collected from 207 AA brain donors, including 125 individuals with pathologically confirmed AD and 82 controls. These samples came from 14 NIH-funded AD Research Centers across the United States.
ADAMTS2 stood out as the most significantly differentially expressed gene in this group. It also ranked first in an independent study (medrxiv.org/content/10.1101/2024.11.12.24317218v1) conducted by the same researchers using brain tissue from a much larger group of EA individuals. That study compared people with confirmed Alzheimer's pathology who showed clinical symptoms before death with individuals who had the same pathology but remained cognitively resilient.
"To our knowledge, this is the first time in similarly designed AD genetics studies that the most significant finding was the same in both white and African Americans," said corresponding author Lindsay A. Farrer, PhD, chief of biomedical genetics at the school.
Implications for Understanding Alzheimer's Risk
The researchers say the findings represent a meaningful advance in understanding the genetic foundations of Alzheimer's risk in African Americans. Previous evidence suggests that most known AD risk variants tend to be population-specific or occur at different frequencies across groups.