Genetic diversity in focus: New studies reveal risk factors for Alzheimer's disease

Genetic diversity in focus: New studies reveal risk factors for Alzheimer's disease

An international study on the genetic predisposition to Alzheimer's shows groundbreaking results that could make a significant contribution to understanding the disease. The research, coordinated by the European Alzheimer's and Dementia Biobank (EADB), represents the first global analysis of polygenic risk scores (PRS) related to Alzheimer's disease. This study includes data from populations from Europe, Asia, Africa, North America, South America and Australia, underscoring its global relevance.

The research teams led by Professor Dr. Dr. Alfredo Ramirez from the University of Cologne identified two genetic signatures for complex forms of Alzheimer's disease. While one signature is strongly dominated by apolipoprotein E (APOE), the other indicates that around 75 other genetic variants play a role. What is particularly noteworthy is that the second signature is consistent across all populations studied, suggesting a common biological mechanism. These results were published in the scientific journal Nature Genetics published.

Genetic diversity and precision medicine

The findings on genetic diversity are particularly relevant to Latin American populations. Interestingly, the results show differences in the effect of the APOE gene, which contributes to the varying risks in different populations. The study's genome-wide association studies (GWAS) have shown that PRSs are specific to Alzheimer's disease, but not to dementia in general. These specific risk scores identify individuals at high genetic risk and could be useful in clinical trials by specifically selecting high-risk groups for further study.

However, the relevance of PRS extends beyond genetic research. These scores quantify the risk resulting from different genetic variants and can help develop personalized treatment approaches. Precision in therapy is critical, particularly with the more than 6 million older adults in the United States suffering from Alzheimer's disease and memory loss and cognitive impairment.

Risk factors and challenges

Alzheimer's disease is not just a genetic disease. Various risk factors play a crucial role. These include age, certain genetic factors and comorbidities such as high blood pressure, elevated cholesterol levels and high homocysteine ​​levels. Genetic variants in the ApoE gene are particularly noteworthy here. While one variant offers some protection, another is known to significantly increase the risk.

Additionally, research in this area faces challenges. It is criticized that many PRS analyzes have so far been based on data from European ancestry, which increases health inequalities. Currently, diversity in PRS studies comprises just 4% of non-European samples. In the long term, the development of pathway-specific PRS is required to enable a better understanding of disease development and to improve predictive capabilities. This is particularly important because Alzheimer's disease often affects different populations differently.

The results of this comprehensive study could represent a significant advance in the precision of the diagnosis and treatment of Alzheimer's disease. Greater consideration of genetic diversity and an interdisciplinary approach are essential to develop targeted treatment strategies and better understand the burden of disease in diverse populations.