The prevalence of Alzheimer's disease (AD) continues to rise due to the increasing aging population. Among the various genetic factors associated with AD, apolipoprotein E (ApoE), a lipid transporter, stands out as the primary genetic risk factor. Specifically, individuals carrying the ApoE4 allele exhibit a significantly higher risk. However, emerging research indicates that dietary factors play a prominent role in modifying the risk of AD. Docosahexaenoic acid (DHA), a prominent ω-3 fatty acid, has garnered considerable attention for its potential to ameliorate cognitive function. The intricate interplay between DHA and the ApoE genotype within the brain, which may influence DHA's utilization and functionality, warrants further investigation. This review meticulously examines experimental and clinical studies exploring the effects of DHA on cognitive decline. Special emphasis is placed on elucidating the role of ApoE gene polymorphism and the underlying mechanisms are discussed. These studies suggest that early DHA supplementation may confer benefits to cognitively normal older adults carrying the ApoE4 gene. However, once AD develops, ApoE4 non-carriers may experience greater benefits compared to ApoE4 carriers, although the overall effectiveness of DHA supplementation at this stage is limited. Potential mechanisms underlying these differential effects may include accelerated DHA catabolism in ApoE4 carriers, impaired transport across the blood-brain barrier (BBB), and compromised lipidation and circulatory function in ApoE4 carriers. Thus, the supplementation of DHA may represent a potential intervention strategy aimed at compensating for these deficiencies in ApoE4 carriers prior to the onset of AD.

由于人口老龄化的加剧，阿尔茨海默病（AD）的患病率持续上升。在与 AD 相关的各种遗传因素中，载脂蛋白 E (ApoE)（一种脂质转运蛋白）是主要的遗传风险因素。具体来说，携带 ApoE4 等位基因的个体表现出明显更高的风险。然而，新兴研究表明饮食因素在改变 AD 风险方面发挥着重要作用。二十二碳六烯酸 (DHA) 是一种重要的 ω-3 脂肪酸，因其改善认知功能的潜力而受到广泛关注。大脑内 DHA 和 ApoE 基因型之间错综复杂的相互作用可能会影响 DHA 的利用和功能，值得进一步研究。这篇综述仔细审查了探索 DHA 对认知能力下降影响的实验和临床研究。特别强调阐明 ApoE 基因多态性的作用并讨论其潜在机制。这些研究表明，早期补充 DHA 可能会给认知正常、携带 ApoE4 基因的老年人带来益处。然而，一旦 AD 发展，尽管现阶段补充 DHA 的整体效果有限，但 ApoE4 非携带者可能会比 ApoE4 携带者获得更大的益处。这些差异效应的潜在机制可能包括 ApoE4 携带者 DHA 分解代谢加速、跨血脑屏障 (BBB) 运输受损以及 ApoE4 携带者脂化和循环功能受损。因此，补充 DHA 可能是一种潜在的干预策略，旨在补偿 AD 发病前 ApoE4 携带者的这些缺陷。