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.

Introduction: 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. Methods: 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 ( Results: Compared with the noncarriers, the APOE4 carriers had significantly lower scores in the "recalling five objects" sub-item 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. Conclusion: 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.