In a recent study funded by the National Institute on Aging (NIA) and published in the journal Alzheimer’s & Dementia, researchers discovered both new and known genetic risk factors for Alzheimer’s disease by examining the genetic makeup of a select group of individuals with Ashkenazi Jewish heritage. Their findings suggest that focusing on the genomes of Ashkenazi Jews and similar “genetic founder” populations may shed light on the genetic underpinnings of Alzheimer’s.
Ashkenazi Jews trace their roots to Jewish communities established in Central and Eastern Europe during the medieval period. For centuries, these communities remained culturally segregated from their non-Jewish neighbors, leading to a genetically unique population. This “founder effect” has resulted in a higher prevalence of certain hereditary diseases and cancers among Ashkenazi Jews. The study proposed that identifying genetic risk factors for Alzheimer’s may be more straightforward within this group compared to the more genetically diverse European populations.
Directed by a team from Boston University, the study analyzed data from three extensive Alzheimer’s disease genetic studies, encompassing over 80,000 participants of European origin. Of these, over 6,500 were of Ashkenazi Jewish descent, with roughly 2,800 diagnosed with Alzheimer’s and about 3,700 without the disease.
In the comparative analysis between individuals diagnosed with Alzheimer’s and those without it, the research team identified not only familiar genetic risk factors like the variants in the APOE and TREM2 genes but also found that the links with APOE were notably strong in spite of the limited size of the sample group. Additionally, they pinpointed several potential novel risk factors exhibiting marginal levels of association with Alzheimer’s disease. For instance, one such factor was associated with the RAB3B gene, which plays a critical role in dopamine release, a pivotal neurotransmitter in brain function.
Validation of these findings emerged from subsequent analysis of brain tissue post-mortem, reinforcing the premise that the genetic variants highlighted by the research indeed contribute to the risk of Alzheimer’s disease. The research team observed that the genetic homogeneity of the study population was instrumental in unveiling new genetic contributors that might remain obscured in a more genetically varied group.
These initial discoveries lay the groundwork for future investigations, which are essential for corroborating these results and possibly detecting other genetic factors linked to Alzheimer’s among Ashkenazi Jews and other similar isolated communities historically.