【文献解读】
阿尔茨海默病(AD)是一种神经退行性疾病，它的主要危险因素是衰老，主要遗传风险因素是载脂蛋白E基因中的一种变体，称为APOE4。2019年2月，发表在期刊《FASEB Journal》的文章中表示DHA 可以预防APOE4相关的阿尔茨海默病。
多项研究表明，补充每天2克DHA可以减慢AD的认知衰退的进展。研究人员发现，尽管大脑中富含DHA，但神经元缺乏合成它的能力，虽然星形胶质细胞能够从植物ω-3脂肪酸α-亚麻酸合成 DHA，但大多数DHA必须从饮食中获得并从血浆穿过血脑屏障进入大脑，而大脑中存在的APOE4会导致血脑屏障被破坏。进一步的研究发现，溶血磷脂酰胆碱 DHA（DHA-lysoPC）通过血脑屏障的外膜小叶转运通过被动扩散，不会受到APOE4的影响，从而降低 AD 风险。
注：将游离DHA和DHA-lysoPC运输到大脑中。游离DHA与血浆中的白蛋白分离，并通过被动扩散沿 血脑屏障的外膜小叶运输。星形胶质细胞中产生的APOE3在维持紧密连接方面发挥作用，使血脑屏障的外膜小叶保持完整。DHA-lysoPC与白蛋白分离，并通过含有主要促进剂超家族结构域的MFSD2A沿着血脑屏障的内膜小叶运输，MFSD2A利用钠的电化学势将DHA-lysoPC转移到大脑中。
迄今为止，所有单独或一起评估DHA对具APOE4等位基因AD患者认知功能和大脑形态影响的临床试验都使用了鱼油补充剂，这些补充剂不含磷脂形式的 DHA。当DHA以磷脂形式食用时，更多的DHA以DHA-lysoPC的形式出现在血浆中，这可能会更好地通过血脑屏障。
【文献节选】
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer’s disease (AD) and ameliorates symptoms. The apolipoprotein E (APOE)4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood–brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.—Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer’s disease.