Genes implicated in Alzheimer's studies in African Americans

The largest gene-expression study in African Americans with Alzheimer's disease reveals overexpression of a gene also implicated in those with white European ancestry.

Researchers from Boston University Chobanian and Avedisian School of Medicine, Massachusetts, looked at RNA sequencing data from post-mortem brain tissue from 207 donors: 125 confirmed Alzheimer's disease cases and 82 controls. ADAMTS2 was the gene with the most significant gene expression differences between cases and controls, being 1.5 times more expressed in the brain of patients with Alzheimer's disease. ADAMTS2 is a gene involved in the production of collagen, which helps provide structure to many body tissues. This gene has also ranked among the top genes with highest expression differences in patients with Alzheimer's disease, in a European ancestry population, according to a previous study from the same group.

'The fact that expression of ADAMTS2 is significantly and substantially higher in brain tissue from both [white and black people] with Alzheimer's disease not only points to a shared biological process leading to Alzheimer's disease, but also elevates the priority of further research involving this gene which could determine its suitability as a potential therapeutic target,' said Professor Lindsay Farrer, chief of biomedical genetics at the Boston University Chobanian and Avedisian School of Medicine, and senior author of the study published in the journal Alzheimer's and Dementia.

According to the researchers, a total of 482 of the 33,611 genes studied were differentially expressed in cases when compared to controls, in the African American population. Out of these, 174 had higher and 308 had lower expression in Alzheimer's disease cases than controls. The study showed that 65 of these genes were differentially expressed in the same direction in both the African American population and the European ancestry population. Meaning that genes that were overexpressed in one population were also overexpressed in the other, and vice-versa.

A link to several genes involved in the mitochondrial energy production pathways was also observed. According to the authors, this corroborates other studies that have linked mitochondrial energy pathways to Alzheimer's disease and suggest that this pathway is a potential druggable target for Alzheimer's disease treatment and prevention.

The authors concluded that: 'The inclusion of African American participants in Alzheimer's disease research is important not only to ensure that predictions made based on genetic and 'omic data are accurate in this population, but also because of the potential it will lead to new and important advances in knowledge about Alzheimer's disease risk that will benefit everyone.'