Scientists Discover New Genetic Risk Factors for Alzheimer's

The findings are unique to the Ashkenazi Jewish population in Eastern Europe but could help researchers identify Alzheimer-related biomarkers, leading to the development of new therapeutic targets.

For hundreds of years, the Ashkenazi Jewish community in Eastern Europe remained genetically isolated from neighboring communities. As a result, scientists can trace this population's genetic lineage to a small group of ancestors, making them more genetically consistent.

Gene-associated signals for specific diseases may be more pronounced in populations with similar genetic profiles, which could help identify novel genes associated with certain conditions, including Alzheimer's disease (AD).

With this in mind, scientists from Boston University Chobanian & Avedisian School of Medicine conducted a genome-wide investigation in 3,500 people with an almost exclusive Ashkenazi Jewish ancestry to identify potential genetic risk factors for AD.

The study, published on June 1 in Alzheimer's & Dementia, analyzed the genetic data from Ashkenazi Jewish participants with and without AD and identified two previously known genetic risk factors. These include a gene involved in transporting cholesterol and other fats in the blood called APOE, and TREM2, a pattern-recognizing receptor on myeloid cells that plays a role in amyloid plaques.

However, they also found new AD-associated risk factors, including RAB3, SMAP2, ZNF890P, SPOCK3, and GIPR, which demonstrates how genome-wide studies in genetically similar populations can help discover AD-related gene variants.

In a Boston University news release, Lindsay A. Farrer, Ph.D., corresponding author and chief of biomedical genetics, says, "Our study illustrates the greatly increased power for detection of genetic associations in communities like Ashkenazi Jews who trace their lineage to a relatively small group of ancestors. In such communities, disease-associated variants may be much more frequent compared to samples ascertained from large, mixed populations."

Though most of the genetic variants were only found in the Ashkenazi Jewish participants, the researchers suggest that these findings are likely applicable to other populations. In addition, the results provide evidence that conducting genome-wide association studies in genetically homogeneous communities can lead to the discovery of genetic associations to specific diseases.