Researchers have identified the gene ADAMTS2 as significantly more active in brain tissue from African Americans with Alzheimer's disease, marking a potential shared biological pathway across racial groups. This finding emerges from the largest study of its kind using brain samples from over 200 African American donors. The gene's prominence also appeared in a separate analysis of White individuals, suggesting broader implications for treatment.
Alzheimer's disease disproportionately affects African Americans, striking them at roughly twice the rate of White or European-ancestry individuals in the U.S. Factors like unequal healthcare access, educational disparities, and higher incidences of cardiovascular disease and diabetes contribute to this gap. However, genetic research has often overlooked African American populations due to small sample sizes in prior studies.
In a landmark effort, scientists at Boston University Chobanian & Avedisian School of Medicine examined gene expression in post-mortem prefrontal cortex tissue from 207 African American brain donors. Of these, 125 had pathologically confirmed Alzheimer's, while 82 served as controls. The samples were sourced from 14 NIH-funded Alzheimer's Research Centers nationwide.
The analysis revealed numerous genes differing between the groups, many previously unlinked to the disease. The standout was ADAMTS2, whose activity was 1.5 times higher in Alzheimer's-affected tissue compared to controls. Remarkably, this gene ranked highest in an independent study by the same team, which analyzed brain tissue from a larger cohort of White individuals—comparing those with Alzheimer's pathology and symptoms to resilient cases.
"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 Lindsay A. Farrer, PhD, chief of biomedical genetics at the school and corresponding author.
Farrer highlighted the discovery's potential: "The fact that expression of ADAMTS2 is significantly and substantially higher in brain tissue from both Whites and Blacks with AD not only points to a shared biological process leading to AD, but also elevates the priority of further research involving this gene which could determine its suitability as a potential therapeutic target."
While many Alzheimer's risk variants vary by population, this overlap suggests common mechanisms. The study, published online in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, was funded by multiple NIH grants but independent of funder influence.
This advance could refine understanding of Alzheimer's genetics in underrepresented groups, paving the way for targeted therapies.
