Global Study Reveals Genetic Risk Factors for Alzheimer's Disease

A groundbreaking international study spearheaded by the European Alzheimer's and Dementia Biobank (EADB) consortium has unveiled significant insights into the genetic risk factors associated with Alzheimer's disease (AD) across diverse global populations. This research, published in the journal Nature Genetics on June 18, 2025, marks the first comprehensive analysis of polygenic risk scores (PRS) in relation to AD susceptibility, examining various demographic groups from continents including Europe, Asia, Africa, North America, South America, and Australia.

The study's findings, led by Professor Dr. Dr. Alfredo Ramirez from the University of Cologne, reveal two distinct genetic signatures linked to the most common and complex forms of Alzheimer's disease. One of these signatures is primarily influenced by the apolipoprotein E (APOE) gene, while the other involves an intricate interplay of approximately 75 additional genetic variants. This latter pattern demonstrates remarkable consistency across populations, indicating a shared biological mechanism responsible for a substantial proportion of AD risk worldwide.

The research team utilized summary statistics from the latest Genome-Wide Association Study (GWAS) on Alzheimer's disease, published in 2022, to create the PRS. The statistics provided a detailed genome-wide list of genetic variants associated with AD and their respective contributions to risk. By categorizing individuals into AD cases and healthy controls, the researchers assessed the efficacy of the PRS in distinguishing between the two groups.

One of the pivotal discoveries of the study is the variability of the APOE gene's impact among different populations. This variability is attributed to currently unidentified genetic differences within the genomic region housing the APOE gene, suggesting its central role in the differing prevalence and risk levels observed across ethnic and regional groups. Notably, polygenic risk scores were found to be specific to Alzheimer's disease rather than dementia in general, reinforcing the necessity for precise clinical diagnoses and highlighting the potential of PRS as a tool to enhance clinical trials.

Professor Ramirez emphasized the importance of inclusive science in addressing health disparities, stating, "In a time when immigration and diversity are increasingly politicized, this study underscores the importance of inclusive science. Most research has focused on individuals of European ancestry, raising concerns about generalizability and equity in understudied populations from low- and middle-income countries with different ethnicities." He further highlighted that the study illustrates how global collaboration and attention to genetic diversity can deepen scientific understanding and promote health equity.

The implications of this research extend beyond academic interest; they represent a critical move towards precision medicine, where treatment and prevention strategies can be tailored to the genetic profiles of individuals and populations alike. As demographics continue to shift and become more genetically diverse, understanding shared and population-specific risk factors becomes increasingly vital.

In conclusion, this study significantly advances the understanding of the genetic components of Alzheimer's disease, paving the way for more effective and targeted therapeutic strategies. The research is viewed as a major stride in the global fight against Alzheimer's, with the EADB consortium committed to further exploring genetic diversity in AD and its implications for health equity.