title: Fatty acid metabolism in carriers of apolipoprotein E epsilon 4 allele: is it contributing to higher risk of cognitive decline and coronary heart disease?
abstract: Apolipoprotein E (ApoE) is a protein playing a pivotal role in lipid homeostasis since it regulates cholesterol, triglyceride and phospholipid metabolism in the blood and the brain. APOE gene regulates the expression of this protein and has three different alleles: ε2, ε3 and ε4. Carrying an APOE4 allele is recognised as a genetic risk factor of late-onset Alzheimer's disease (LOAD) and coronary heart disease (CHD). Consuming fatty fish, rich in long chain omega-3 fatty acids (LC omega-3), seems to be associated with risk reduction of developing LOAD and CHD but this link seems not to hold in APOE4 carriers, at least in LOAD. In CHD trials, APOE4 carriers supplemented with LC omega-3 were categorized as differential responders to the treatment with regards to CHD risk markers. This is potentially because fatty acid metabolism is disturbed in APOE4 carriers compared to the non-carriers. More specifically, homeostasis of LC omega-3 is disrupted in carriers of APOE4 allele and this is potentially because they β-oxidize more LC omega-3 than the non-carriers. Therefore, there is a potential shift in fatty acid selection for β-oxidation towards LC omega-3 which are usually highly preserved for incorporation into cell membranes.
authors.affiliation: Research Center on Aging, Health and Social Services Centre-University Institute of Geriatrics of Sherbrooke, Department of medicine, Université de Sherbrooke, 1036 Belvédère Sud, Sherbrooke, J1H 4C4, Canada. raphael.chouinard-watkins@usherbrooke.ca.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Chouinard-Watkins
authors.affiliation: Research Center on Aging, Health and Social Services Centre-University Institute of Geriatrics of Sherbrooke, Department of medicine, Université de Sherbrooke, 1036 Belvédère Sud, Sherbrooke, J1H 4C4, Canada. Melanie.plourde2@usherbrooke.ca.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Plourde
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism*; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005399:Fishes; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D015525:Fatty Acids, Omega-3