title: Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele.
abstract: Carrying the apoE ε4 allele (E4+ ) is the most important genetic risk for Alzheimer’s disease. Unlike non-carriers (E4- ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+ v. E4-. A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4-. In E4+, mean plasma [13C]DHA was 31% lower than that in E4-, and cumulative b-oxidation of [13C]DHA was higher than that in E4- 1–28 d post-dose (P ≤0·05). A genotype x time interaction was detected for cumulative b-oxidation of [13C]DHA (P ≤ 0·01). The whole-body half-life of [13C]DHA was 77% lower in E4+ compared with E4- (P ≤0·01). In E4+ and E4-, the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117% steeper in E4+ compared with E4- (P ≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study.
authors: Research Center on Aging, Health and Social Services Centre, University Institute of Geriatrics of Sherbrooke, 1036 Belvédère Sud, Sherbrooke, QC, Canada J1H 4C4.
authors: R
authors: R
authors: Chouinard-Watkins
authors: C
authors: C
authors: Rioux-Perreault
authors: M
authors: M
authors: Fortier
authors: J
authors: J
authors: Tremblay-Mercier
authors: Y
authors: Y
authors: Zhang
authors: P
authors: P
authors: Lawrence
authors: M C
authors: MC
authors: Vohl
authors: P
authors: P
authors: Perron
authors: D
authors: D
authors: Lorrain
authors: J T
authors: JT
authors: Brenna
authors: S C
authors: SC
authors: Cunnane
authors: M
authors: M
authors: Plourde
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics*; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics*; D004032:Diet; D004041:Dietary Fats / Q000097:blood / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005399:Fishes; D005838:Genotype; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D015227:Lipid Peroxidation / Q000235:genetics*; D008297:Male; D010084:Oxidation-Reduction
chemical_list: D053327:Apolipoprotein E4; D002247:Carbon Isotopes; D004041:Dietary Fats; D002245:Carbon Dioxide; D004281:Docosahexaenoic Acids