Factors Influencing Alzheimer’s Disease Risk: Whether and How They are Related to the APOE Genotype

 Rong Zhang1 • Xiaojiao Xu1 • Hang Yu1 • Xiaolan Xu1 • Manli Wang1 • Weidong Le1
1 Institute of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease featuring progressive cognitive impairment. Although the etiology of late-onset AD remains unclear, the close association of AD with apolipoprotein E (APOE), a gene that mainly regulates lipid metabolism, has been firmly established and may shed light on the exploration of AD pathogenesis and therapy. However, various confounding factors interfere with the APOE-related AD risk, raising questions about our comprehension of the clinical findings concerning APOE. In this review, we summarize the most debated factors interacting with the APOE genotype and AD pathogenesis, depict the extent to which these factors relate to APOEdependent AD risk, and discuss the possible underlying mechanisms.
Apolipoprotein E; Alzheimer’s disease; Ethnicity; Diet; Geographic factor; Aging; Gender