African Ancestry Reduces Risk From APOE Gene in Alzheimer’s

The APOE ε4 allele is strongly associated with Alzheimer’s disease risk, but there is variability in the risk effect across populations. A study presented at the American Academy of Neurology 2022 annual meeting aimed to identify genetic loci that show a protective effect in patients with an African ancestral background compared with other backgrounds.

In this exclusive MedPage Today video, lead study author Farid Rajabli, MD, of the University of Miami Miller School of Medicine in Florida, explains the results of the study.

Following is a transcript of his remarks:

The APOE gene is a major risk factor in late-onset Alzheimer’s disease. First it was identified by Dr. [Margaret] Pericak-Vance and her colleagues, and they used the European ancestor population and later expanded to other populations. Results showed that there’s a variation of the effect size of APOE risk across the populations.

So, to follow up and answer the question of why there’s a difference across the populations, three independent studies were performed and they use mixed populations to look at this difference. So, why mixed populations? Because a mixed population has more than one ancestor background; for example, African Americans are a mixed population with African and European background.

So, the question was, is really the difference of the effect size because of the ancestral background of this APOE gene? And they assessed this ancestor background, and they found that the individuals who inherited their APOE gene from European ancestors have higher risk than individuals who inherited this APOE gene from African ancestors.

In this study, we follow up this locus ancestor finding, and we tried to answer the other question, what exactly about this ancestor background is different and what lowered the risk of the APOE gene in these African populations? We used around 6,500 African-American individuals, and we assessed the region around the APOE gene, and looked at all the genetic factors, which can affect the risk of the APOE. And we identified the locus, which is located around the 2-Mb next to the APOE gene, and it reduced the risk of APOE in African ancestor populations.

We then replicated our results in two different populations, [including] a Nigerian population, which has 100% of African ancestor background. And also we looked at this in a Hispanic population, that also has the African ancestor background. And we have replicated our results.

We observed a similar trend in a European population. It didn’t pass the threshold of significance, but the region that we identified was African specific. It was very low frequency in the Europeans. So, this finding is really interesting, as it’s providing a natural protective factor that is of key importance, as it can improve the therapeutics in terms of Alzheimer’s disease treatment.