title: High dietary consumption of trans fatty acids decreases brain docosahexaenoic acid but does not alter amyloid-beta and tau pathologies in the 3xTg-AD model of Alzheimer's disease.
abstract: Dietary consumption of trans fatty acids (TFA) has increased during the 20th century and is a suspected risk factor for cardiovascular diseases. More recently, high TFA intake has been associated with a higher risk of developing Alzheimer's disease (AD). To investigate the impact of TFA on an animal model genetically programmed to express amyloid-beta (Abeta) and tau pathological markers of AD, we have fed 3xTg-AD mice with either control (0% TFA/total fatty acid), high TFA (16% TFA) or very high TFA (43% TFA) isocaloric diets from 2 to 16 months of age. Effects of TFA on plasma hepatic enzymes, glucose and lipid profile were minimal but very high TFA intake decreased visceral fat of non-transgenic mice. Importantly, dietary TFA increased brain TFA concentrations in a dose-related manner. Very high TFA consumption substantially modified the brain fatty acid profile by increasing mono-unsaturated fatty acids and decreasing polyunsaturated fatty acids (PUFA). Very high TFA intake induced a shift from docosahexaenoic acid (DHA, 22:6n-3) toward n-6 docosapentaenoic acid (DPA, 22:5n-6) without altering the n-3:n-6 PUFA ratio in the cortex of both control and 3xTg-AD mice. Changes in levels of Abeta(40), Abeta(42), tau protein, phosphorylated tau protein and synaptic markers were not statistically significant in the three groups of 3xTg-AD mice, despite a trend toward decreased insoluble tau in very high TFA-fed 3xTg-AD animals. In summary, TFA intake modulated brain fatty acid profiles but had no significant effect on major brain neuropathological hallmarks of AD in an animal model.
authors.affiliation: Faculty of Pharmacy, Université Laval, 1050 de la Médecine Avenue, Québec, Québec, Canada G1V 0A6.
authors.forename: A
authors.initials: A
authors.lastname: Phivilay
authors.forename: C
authors.initials: C
authors.lastname: Julien
authors.forename: C
authors.initials: C
authors.lastname: Tremblay
authors.forename: L
authors.initials: L
authors.lastname: Berthiaume
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: Y
authors.initials: Y
authors.lastname: Giguère
authors.forename: F
authors.initials: F
authors.lastname: Calon
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D044242:Trans Fatty Acids / Q000008:administration & dosage* / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D053764:Presenilin-1; D044242:Trans Fatty Acids; D016875:tau Proteins; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D000410:Alanine Transaminase