Abstract
APOE (apolipoprotein E) is a key regulator of lipid metabolism and a leading genetic risk factor for Alzheimer's disease. While APOE participates in multiple biological pathways, its roles in diseases are largely due to the mutant protein encoded by APOE-ε4. However, emerging evidence suggests that some noncoding Alzheimer's disease risk variants residing in APOE and its nearby regions exert APOE-ε4-independent risks and modify APOE gene expression. Moreover, intervention strategies targeting APOE are being explored. In this review, we summarize the literature on the genetic risks and roles of APOE in biological systems. Moreover, we propose an integrative approach to evaluate disease risk and tailor interventions to aid research on APOE-associated diseases.
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