Ashkenazi Jews are more likely to suffer from Alzheimer’s, according to a study

Alzheimer’s disease (AD), the most common neurodegenerative disease in the world, affects people of all ethnicities and races.

However, most AD genetic research has been performed in individuals of European ancestry (EA), with a limited number of large-scale genetic studies in other populations.

Over the centuries, Ashkenazi Jews have been almost completely genetically isolated from their non-Jewish neighbors. As a result, researchers at Boston University’s Chobanian & Avedisian School of Medicine hypothesized in a study that some AD susceptibility variants are more frequent and therefore more likely to show statistically significant associations in this group, compared with AE cohorts. much larger and genetically more heterogeneous.

Their study recently appeared in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association under the title, “New loci for Alzheimer’s disease identified by genome-wide association study in Ashkenazi Jews.”

Some rare autosomal recessive disorders (involving any of the 22 numbered pairs of chromosomes found in most human cells) that manifest in childhood, including Tay-Sachs disease, Gaucher disease, familial dysautonomia, Canavan disease, Bloom syndrome, and spinal muscular atrophy, as well as particular genetic mutations that confer a high risk of common disorders, such as early-onset breast cancer and multiple gastrointestinal cancers, are found predominantly or with very high frequency higher in Ashkenazi Jews than in other populations.

A petri dish is seen following an embryo transfer surgery at the Beijing Perfect Family Hospital, in Beijing, China April 6, 2023 (Credit: REUTERS/TINGSHU WANG)

First research on the non-European population

‘Most of the Alzheimer’s disease loci were discovered in individuals of European ancestry,’ the researchers wrote. communities such as Ashkenazi Jews who trace their lineage to a relatively small group of ancestors. In such communities, disease-associated variants may be much more frequent than in ascertained samples from large, mixed populations.

The researchers said the study illustrated the greatly increased power for genetic association detection in communities such as Ashkenazi Jews, who trace their lineage to a relatively small group of ancestors.

“Some genetic association signals for complex diseases like AD are likely to be strongest in founder populations that are relatively genetically homogeneous,” Farrer said.

Transethnic studies have shown that population differences in genetic background can be exploited to make new discoveries that may require a sample size several orders of magnitude larger to achieve similar success studying a single population, according to the study.

“Similarly, studies of small samples of founder populations (ethnic or religious groups whose ancestry can be traced to a small number of ancestors and therefore have a more homogeneous genetic background) have successfully found robust and subsequently validated associations of AD with several genes”. the researchers wrote. Farrer and his colleagues conducted a genome-wide association study for AD in a sample of 3,500 people whose ancestry was almost exclusively Ashkenazi Jewish, including roughly equal numbers of people with AD and cognitively normal individuals who were identified in a much larger group of AE participants in large national AD genetic studies using an approach that compared genetic signatures to members of an Ashkenazi Jewish reference sample.

Researchers have identified several genetic risk factors for AD, including some previously known (APOE, TREM2) and several new ones that are strong biological candidates (RAB3, SMAP2, ZNF890P, SPOCK3, GIPR).

Although some of the findings in Ashkenazi Jews have not been seen in other populations due to the rarity or absence of these genetic variants in those groups, Farrer said he believes the contribution of genes harboring these variants to the biology of AD is probably relevant to other important populations. in the world.

“Future studies focusing on the AD-associated genes identified in this study could lead to the development of novel AD biomarkers and therapeutic targets,” Farrer said.

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