The Impact of APOE Gene Variants in Cardiovascular and Neurodegenerative Diseases

Abstract

Pleiotropic effects of APOE gene variants in multiple disease pathways remain among the biggest puzzles for genetic research. Therefore, this review represents a systematic literature review of new evidence for APOE variants associated with cardiovascular, neurodegenerative, and metabolic disorders in various populations. Accordingly, it was based on the in-depth analysis of international cohort studies, meta-analyses, and population-specific research published within a period of 2022-2024. APOE-related disease risks significantly differed by population, including 12-fold increased risk for AD and 40-50% increased risk for CVD in ε4 carriers compared to ε3 homozygotes. Geographic-specific differences were noted as well, where Scandinavian ε2 carriers enjoyed some unique protective factors, and East Asians exhibited different cardiovascular risk profiles. Gene-environment interactions had a great effect on disease risk alterations: adherence to the Mediterranean diet lowered cardiovascular risk by 35% in ε4 carriers. This review shows common underlying pathophysiological pathways across the various diseases of inflammation and cellular injury responses. The results emphasize the importance of population-specific approaches in both research and practice. Future studies are needed to re-expand genetics into more underrepresented populations, targeted therapeutic approaches, and testing personalized interventions relative to APOE genotype. These findings help in deriving an overall understanding of the role of APOE in multiple disease pathways to develop population-specific therapeutic approaches and risk assessment strategies.