Novel Alzheimer’s Disease genetic risk factors and biological pathways discovered in African American individuals
By Chloe Hilles
Four novel, African-American-specific Alzheimer’s disease risk genes were discovered in a study of African American individuals published in JAMA Neurology. The identification of these risk genes are critical to finding new treatments for Alzheimer’s disease for African American individuals.
Compared to non-Hispanic white people, African American individuals from the same community are approximately two times as likely to develop Alzheimer’s disease. Because the two groups are from the same community, the disparity in disease development between the two groups is not likely to arise from environmental differences.
A new explanation was discovered by a team of collaborators, including Bob Vassar, PhD, director of the Alzheimer’s Disease Research Center (ADRC) P30 Grant and scientific director of behavioral neurology laboratory in the Department of Neurology, attributing the difference to genetic risk factors that are predisposed to the African American population. There are also many risk genes in non-Hispanic white populations as well.
This study used a process called genome-wide association meta-analysis (GWAS) to identify potential new African American Alzheimer’s risk genes. GWAS is a genetic technique that determines which genes in the genome are associated with the disease. Through this process, four novel common African-American-specific Alzheimer's Disease risk genes were discovered:
- intracellular glycoprotein trafficking gene EDEM1,
- immune response gene ALCA,
- glutamatergic receptor membrane recruitment gene GPC6,
- glutamate neurotoxicity gene VRK3.
Other new rare risk genes were discovered called IGF1R, API5, and RBFOX1. However, of the known Alzheimer’s risk genes that are present in non-Hispanic Whites, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were also implicated in African Americans groups.
The bottom line is that genetic analysis strongly suggested that immunity, lipid processing, and intracellular trafficking pathways are the underlying causes of Alzheimer’s disease in African American populations. Immunity, lipid processing, and intracellular trafficking pathways play a role in Alzheimer disease for all individuals, however the new risk genes found affect those pathways only in African American individuals. Additionally, another Alzheimer’s risk gene was found in the kidney system in the African American study groups, which suggests another novel mechanism for Alzheimer’s disease that is specific for African Americans.
The paramount finding of this research suggests why biologically more African Americans have Alzheimer’s disease than white people: a genetic risk factor.
"Genetic differences could indicate variations in disease mechanisms that could represent new drug targets specific for African Americans for therapeutic development,” Vassar said. “Much more research on these mechanisms will be necessary before this knowledge could potentially be translated into African American-specific treatments."