Global Research Identifies Genetic Risk Factors for Alzheimer's Across Diverse Populations

A comprehensive international study, led by the European Alzheimer's and Dementia Biobank (EADB) consortium, has provided new insights into how genetic risk factors for Alzheimer's disease (AD) vary across the globe. This groundbreaking research marks the first worldwide investigation into polygenic risk scores (PRS) and their association with the likelihood of developing Alzheimer's. The study analyzed data from populations across Europe, Asia, Africa, North and South America, and Australia, revealing both shared and population-specific genetic influences.

A key discovery of the research is the identification of two distinct genetic signatures linked to common, complex forms of Alzheimer's. One signature is predominantly influenced by the apolipoprotein E (APOE) gene, known to significantly impact AD risk. The other involves a combination of approximately 75 additional genetic variants, which appear to act in concert. Notably, this latter pattern shows consistency across different populations, suggesting a universal biological mechanism underlying a substantial portion of Alzheimer's risk worldwide.

The study, published in Nature Genetics, utilized data from the latest Genome-Wide Association Study (GWAS) on Alzheimer’s, integrating summary statistics describing genetic variants associated with the disease. The researchers found that while the effect of APOE varies considerably across populations, the polygenic risk score that encompasses the other variants remains informative universally. This variability in APOE’s influence is likely due to genetic differences within the region containing the gene, which varies among ethnicities and regions.

Professor Dr. Alfredo Ramirez from the University of Cologne and his team, who have long studied Alzheimer's genetics especially in underrepresented populations such as Latin America, highlight the importance of this research for advancing precision medicine. The findings underscore the need to consider genetic diversity in disease risk assessments and treatment strategies.

By comparing populations worldwide, scientists are better equipped to understand which genetic factors are broadly shared and which are population-specific. This knowledge is vital for developing targeted interventions and improving the accuracy of clinical diagnoses. The significance of polygenic risk scores (PRS) as a tool for identifying high-risk individuals is emphasized, especially for enhancing clinical trials by selecting suitable candidates while excluding those with diagnostic uncertainty.

Ramirez emphasized that inclusive, global science is crucial for health equity, especially as most genetic research has historically focused on European populations. His work advocates for more diverse genetic studies to ensure all populations benefit from scientific advances. Ultimately, this research contributes significantly to understanding Alzheimer’s disease's complex biology and marks a major step toward personalized, equitable medicine in combating this growing global health challenge.