Abstract
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 APOE -dependent AD risk, and discuss the possible underlying mechanisms.