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.

APOE（载脂蛋白 E）是脂质代谢的关键调节剂，也是阿尔茨海默病的主要遗传风险因素。虽然APOE参与多种生物学途径，但其在疾病中的作用主要是由于 APOE-ε4 编码的突变蛋白。然而，新出现的证据表明，存在于APOE及其附近区域的一些非编码阿尔茨海默病风险变体发挥APOE -ε4 独立风险并改变APOE基因表达。此外，正在探索针对APOE的干预策略。在这篇综述中，我们总结了有关APOE的遗传风险和作用的文献在生物系统中。此外，我们提出了一种综合方法来评估疾病风险并定制干预措施以帮助研究APOE相关疾病。