Alzheimer’s disease (AD) affects African Americans at nearly twice the rate of White or European-ancestry (EA) individuals in the United States. Researchers believe this difference is partly due to social and environmental factors, including unequal access to healthcare, differences in education quality, and biases in diagnostic testing. In addition, African Americans face higher rates of conditions such as cardiovascular disease and diabetes, which are known risk factors for Alzheimer’s. These overlapping issues highlight how both biology and social conditions contribute to the higher burden of AD in this population.
Previous studies have explored how genes behave differently in the brains of people with Alzheimer’s disease compared to those without it. This is often done by measuring gene expression, which shows how active a gene is in producing its protein. However, most of these studies have focused on people of European ancestry or mixed backgrounds. When African Americans were included, their numbers were usually too small to allow meaningful conclusions about this group. As a result, scientists have had a limited understanding of the genetic and molecular features of Alzheimer’s disease in African American individuals.
A new study from Boston University’s Chobanian & Avedisian School of Medicine has changed that. In the most extensive investigation yet of Alzheimer’s disease using brain tissue from African American donors, researchers identified many genes that were significantly more or less active in people with Alzheimer’s compared to those without. Importantly, many of these genes had not previously been linked to the disease in other genetic studies. One of the most striking discoveries was a 1.5-fold increase in the activity of a gene called ADAMTS2 in the brains of people who had autopsy-confirmed Alzheimer’s disease.
The research team collected post-mortem prefrontal cortex samples from 207 African American donors through 14 NIH-funded Alzheimer’s Disease Research Centres across the country. Of these, 125 had Alzheimer’s disease confirmed by pathology, and 82 did not. When the team compared gene expression levels between the two groups, ADAMTS2 stood out as the most significantly different gene. Interestingly, in a separate and much larger study conducted by the same team using brain tissue from European-ancestry donors, ADAMTS2 was again identified as the top-ranked gene associated with Alzheimer’s. This suggests that ADAMTS2 plays an important role in the disease, regardless of ancestry.
“This is the first time that two parallel studies—one in White and one in African American populations—have identified the same most significant gene,” said Dr Lindsay A. Farrer, chief of biomedical genetics at Boston University. He explained that this finding is rare in Alzheimer’s research, as most genetic variants linked to the disease tend to differ between populations. The shared increase in ADAMTS2 expression suggests a standard biological process that contributes to Alzheimer’s across groups. According to the researchers, this discovery could be key to understanding disease mechanisms that are not limited to one ancestry.
The study represents a significant step forward in uncovering the genetics of Alzheimer’s disease in African Americans, a group often underrepresented in medical research. It also reinforces the need to study diverse populations to gain a more complete picture of how Alzheimer’s develops. The consistent link to ADAMTS2 across both African American and European-ancestry groups makes this gene a promising candidate for future research and possibly new treatment strategies. By broadening the diversity of study participants, scientists move closer to understanding the whole biological landscape of Alzheimer’s disease and developing therapies that work for everyone.
More information: Lindsay A. Farrer et al, Novel differentially expressed genes and multiple biological pathways for Alzheimer’s disease identified in brain tissue from African American donors, Alzheimer’s & Dementia. DOI: 10.1002/alz.70629
Journal information: Alzheimer’s & Dementia Provided by Boston University School of Medicine
