Supplementary Material for: Impact of the apolipoprotein E ε4 allele on cognition and omega-3 fatty acid levels in the plasma membrane of red blood cells in healthy elderly Japanese population

The ε4 allele of the apolipoprotein E (APOE4) gene is a well-known risk factor for the onset and development of late-onset Alzheimer’s disease (AD). Lipid metabolism also plays a key role in AD. However, data on the association between APOE4, cognitive function, and blood lipid metabolism, particularly fatty acid metabolism, in the healthy elderly Japanese population are lacking. To address this issue, we analyzed the baseline data of 506 healthy elderly Japanese individuals (mean age: 73 ± 0.4 years) from Shimane Prefecture, Japan, who participated in six intervention trials conducted between 2008 and 2020. Among them, participants with mild cognitive impairment (MCI) were divided into the following two groups: APOE4 carriers (n = 104) and non-carriers (n = 321). Compared with the non-carriers, the APOE4 carriers had significantly lower scores in the “Recalling five objects” subitem of Hasegawa’s Dementia Scale—Revised and longer total times in the Cognitive Assessment for Dementia iPad version. The ratio of docosahexaenoic acid (DHA) to arachidonic acid was significantly decreased, and the erythrocyte eicosapentaenoic acid (EPA) and DHA levels tended to be reduced in APOE4 carriers. These findings suggest a possible association between the APOE4 allele and reduced erythrocyte EPA and DHA levels, even in healthy elderly Japanese individuals with high ω-3 fatty acid intake. Such alterations in lipid metabolism may be linked to cognitive vulnerability in older adults and individuals with MCI.

载脂蛋白E ε4等位基因（apolipoprotein E ε4, APOE4）是公认的晚发型阿尔茨海默病（late-onset Alzheimer’s disease, AD）发生与进展的危险因素。脂质代谢在AD的发病机制中同样扮演关键角色。然而，目前针对日本健康老年人群中APOE4、认知功能与血脂代谢，尤其是脂肪酸代谢三者间关联的研究数据仍较为匮乏。为填补这一研究空白，本研究对2008年至2020年间参与六项干预试验的506名日本岛根县健康老年个体的基线数据展开分析，该队列人群的平均年龄为73±0.4岁。其中，伴有轻度认知障碍（mild cognitive impairment, MCI）的参与者被划分为两组：APOE4携带者（n=104）与非携带者（n=321）。与非携带者相比，APOE4携带者在长谷川痴呆量表修订版（Hasegawa’s Dementia Scale—Revised）的“回忆五件物品”分项中得分显著更低，且在iPad版痴呆认知评估量表（Cognitive Assessment for Dementia iPad version）中的总完成时长更长。此外，APOE4携带者的二十二碳六烯酸（docosahexaenoic acid, DHA）与花生四烯酸的比值显著降低，其红细胞二十碳五烯酸（eicosapentaenoic acid, EPA）及DHA水平亦呈下降趋势。上述研究结果表明，即便在ω-3脂肪酸（ω-3 fatty acid）摄入水平较高的日本健康老年人群中，APOE4等位基因仍可能与红细胞EPA及DHA水平降低存在关联。这种脂质代谢异常或与老年人群及轻度认知障碍个体的认知易感性相关。