Roles of gene-environment interaction in development of Alzheimer’s disease: implications in prediction, prevention, and pathogenesis

The late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is driven by both genetic and environmental elements. The apolipoprotein E (APOE) gene is the strongest common genetic determinant, followed by a large and still expanding genetic profile. APOE 4 carriers had an estimated 3 to 12 times increased risk of LOAD. We also estimated that an average of roughly 26% were APOE 4 carriers in global community-dwellers, further highlighting the importance of developing tailored prevention strategies for this specific population, especially considering that no modifying therapies are available for AD. Nonetheless, it is still unclear whether the hereditary predisposition could be modified by the environmental factors. Thus, understanding the gene-environment interactions is of magnificent importance. Therefore, in this study, we are using the database from UK Biobank to explore whether and how modifiable environmental factors can interact with APOE to modulate cognitive functions, imaging markers of brain, amyloid pathologies, and AD risk. Our project will generate an environmental risk factor profile which could be specifically targeted for AD prevention among genetic-high-risk populations. The generated findings will help formulate a highly tailored “cocktail” strategy for multi-domain intervention in randomized clinical trial and also help guide the policy making of precision prevention of AD at the population level.