Alzheimer’s disease (AD) is nearly twice as common in African Americans (AA) in the U.S. compared with people of European ancestry (EA). Social determinants such as varying access to health care, education disparities, testing biases, and higher prevalence of cardiovascular disease and diabetes contribute to this gap.
Most research on gene expression in AD has focused on EA or mixed-ancestry groups, often with too few AA participants to detect significant differences specifically in that population.
In the largest AD investigation using brain tissue from AA donors, researchers at Boston University Chobanian & Avedisian School of Medicine identified many genes—most of which had not been previously linked to AD—that were markedly more or less active in patients versus controls. The most striking observation was a 1.5‑fold increase in expression of the ADAMTS2 gene in autopsy‑confirmed AD cases.
The findings are published in Alzheimer’s & Dementia.
Utilizing samples from 14 research centers, the team compiled gene‑expression data from 207 AA brains (125 AD cases and 82 controls). The gene that differed most dramatically, ADAMTS2, also topped the list in an independent, larger-scale study of EA subjects by the same group.
In that prior EA analysis, also featured in Alzheimer’s & Dementia, expression was compared between clinically symptomatic AD cases and those with the same pathology but preserved cognition.
“To our knowledge, this is the first time that the most significant gene in similarly designed studies is the same in both white and African American populations,” said corresponding author Lindsay A. Farrer, Ph.D., chief of biomedical genetics at the school.
The authors argue this research represents a crucial advance toward understanding the genetic makeup and biological mechanisms that increase AD risk in African Americans, especially given that many known risk variants differ in frequency or effect across populations.
“Although African Americans carry variants in several AD‑related genes, overlap with EA populations is modest, and the specific variants and their influence on risk are often distinct,” explained Farrer.
“The fact that ADAMTS2 expression is profoundly higher in both white and Black brains with AD points to a shared biological pathway and underscores this gene’s potential as a therapeutic target.”