Brain DHA increases in APOE3, but not in APOE4 mice, despite robust brain EPA increase during LPC n-3 supplementation in both genotypes.

In a previous study, we showed that oral supplementation with lysophosphatidylcholine (LPC)-bound omega-3 fatty acids (n-3) increases cortical eicosapentaenoic acid (EPA, C20:5n-3) but not docosahexaenoic acid (DHA, C22:6n-3) in an apolipoprotein E (APOE)- and duration-dependent manner. This may reflect DHA retention in blood-brain interfaces, such as microvessels (MV) and choroid plexus (ChP). The objective of this study was to assess whether LPC n-3 intake over two or four months modulates the lipid composition of MV and ChP in APOE3 and APOE4 mice. APOE3 and APOE4 mice received daily gavage of LPC-bound EPA (21.5 mg/day) and DHA (10.4 mg/day) or sunflower oil (control) for two or four months (n = 5-8 mice per genotype and treatment). Lipids from plasma, frontal cortex (FCx), ChP, and MV were analyzed by liquid chromatography-tandem mass spectrometry. Using principal component analysis, we found that phopholipid levels in plasma, ChP, MV, and FCx were modulated more by the type of oil administered by gavage (LPC n-3-enriched oil vs. sunflower oil) than by APOE genotype or gavage duration. The ChP was the most responsive tissue to n-3 supplementation. Total DHA increased in the FCx of APOE3 mice receiving LPC n-3, but not in APOE4 mice. In contrast, EPA levels were significantly higher across genotypes and biological compartments in n-3-supplemented mice. This study reports higher DHA and EPA concentrations in the brain of APOE3 mice supplemented with LPC n‑3 and reinforces evidence of lower DHA accretion in APOE4 mice. It also identifies the ChP as a major site of n‑3 response.