Gene associated with the development of the disease still has little research with non-European populations

Alzheimer's disease is the most common type of dementia, a syndrome characterized by the progressive deterioration of cognitive functions, which causes problems in memory, functional activities, thinking and behavior, becoming more common with advancing age. While the full set of causes is still unknown, it is known that certain genes can increase the risk of developing Alzheimer's, and a new study indicates that one of them, the APOE gene, may have an impact on an individual's ancestry.

This is a research carried out in partnership between the Laboratory of Pathophysiology of Aging (GEROLAB) of the Faculty of Medicine of the University of São Paulo (FMUSP) and the Department of Genetics at USP. In it, the complex interaction between genetics, lesions in the nervous system tissue and functional cognition was investigated in a sample of 400 individuals affected by Alzheimer's pathology with different levels of severity.

“The results of this research help us to understand how the main genetic factor for Alzheimer's disease, which is Apolipoprotein E, is associated with this condition differently between people who have African ancestry and those who do not have a large amount of that ancestry”, says Claudia Kimie Suemoto, Professor of the Discipline of Geriatrics at FMUSP and researcher at the Faculty's Biobank for Studies on Aging.

Apolipoprotein E is encoded by the APOE gene, which plays a key role in lipid metabolism, and whose APOE4 variation is one of the main recognized genetic factors for the predisposition to the development of dementia.

“It has been known for years that APOE4 is one of the common variants with the greatest effect on Alzheimer's”, says Michel Naslavsky, Professor at the Department of Genetics and Evolutionary Biology at the Institute of Biosciences at USP and first author of the study. “What has recently become evident, thanks to more inclusive studies with non-European populations, is that APOE4 may have an attenuated effect depending on ancestry.” Thus, although this gene appears to have a harmful effect on all population groups, individuals with more African ancestry would be less susceptible to its impact.

Environment and Genetics

According to the medical literature, people with African ancestry tend to have less accumulation of lesions in the nervous system tissue associated with Alzheimer's. However, when these lesions are in large numbers, this ancestry is associated with a worse cognitive ability. In the US, for example, the incidence of dementia is about twice as high in African Americans as in whites and other minorities.

“Most of the differences are due to different environmental exposures”, comments Prof. Naslavsky. “Still, we know that there are genetic distinctions in individuals who declare themselves white and black due to multiple ancestry.” The researcher points out that the complexity increases when analyzing more mixed-race countries, such as Brazil, where many have APOEs of different origins.

Scientists are betting that by identifying the relative role of APOE in each population, it will be possible to better understand the functional changes in the body that occur as a result of Alzheimer's disease.

The next step of the research, according to Prof. Claudia Suemoto, will be “to continue to collect more cases of Alzheimer's to increase the sample and carry out other genetic studies, not only with Apolipoprotein E, but with other candidate risk genes for this disease”.

The study was published September 7, 2022 in the journal Molecular Psychiatry and can be viewed at: https://www.nature.com/articles/s41380-022-01729-x