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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.

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