Associations of ApoE4 status and DHA supplementation on plasma and CSF lipid profiles and entorhinal cortex thickness.
Academic Article
Overview
abstract
BACKGROUND: Apolipoprotein ε allele 4 (APOE4) influences the metabolism of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The entorhinal cortex (EC) area in the brain is affected early in Alzheimer's disease (AD) and is rich in DHA. The purpose of this study is to identify the effect of APOE4 and DHA lipid species on the changes in EC. METHODS: Plasma and CSF lipidomic measurements were obtained from the DHA Brain Delivery Pilot, a randomized clinical trial of DHA supplementation (n=10) vs. placebo (n=12) for six months in non-demented older adults stratified by APOE4 carrier status. Wild C57B6/J mice were fed a high or low DHA diet for 6 months followed by plasma and brain lipidomic analysis. RESULTS: Levels of phosphatidylcholine DHA (PC 38:6) and cholesterol ester DHA (CE 22:6) had the largest increases in CSF following supplementation (p<0.001). DHA within triglyceride (TG) lipids in CSF strongly correlated with the corresponding plasma TG lipids, and differed by APOE4, with carriers having a lower increase than non-carriers. Changes in plasma PC DHA had the strongest association with the change in EC thickness in millimeters, independent of APOE4 status (p=0.007). In mice, a high DHA diet increased PUFAs within brain lipids. CONCLUSION: Our findings demonstrate an exchange of DHA at the CSF-blood barrier and into the brain within all lipid species with APOE genotype having the strongest effect on DHA containing TGs. The correlation of PC DHA with EC suggests a functional consequence of DHA accretion in HDL for the brain.
