High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model

• Published in: Neurobiology of aging 2010-09, Vol.31 (9), p.1516-1531
• Main Authors: Julien, Carl, Tremblay, Cyntia, Phivilay, Alix, Berthiaume, Line, Émond, Vincent, Julien, Pierre, Calon, Frédéric
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - chemically induced; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid-beta; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cofilin; Development. Senescence. Regeneration. Transplantation; Dietary fat; Dietary Fats - adverse effects; Dietary Fats - metabolism; Dietary Fats - pharmacology; Disease Models, Animal; Docosahexaenoic acid; Drebrin; Fatty Acids, Omega-3 - adverse effects; Fatty Acids, Omega-3 - pharmacology; Fundamental and applied biological sciences. Psychology; GFAP; Humans; Internal Medicine; LR11; Mice; Mice, Transgenic; Neurology; PAK; Polyunsaturated fatty acid; Synaptophysin; tau; tau Proteins - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2008.08.022

Abstract To investigate potential dietary risk factors of Alzheimer’s disease (AD), triple transgenic (3xTg-AD) mice were exposed from 4 to 13 months of age to diets with a low n-3:n-6 polyunsaturated fatty acid (PUFA) ratio incorporated in either low-fat (5% w/w) or high-fat (35% w/w) formulas and compared with a control diet. The n-3:n-6 PUFA ratio was decreased independently of the dietary treatments in the frontal cortex of 3xTg-AD mice compared to non-transgenic littermates. Consumption of a high-fat diet with a low n-3:n-6 PUFA ratio increased amyloid-β (Aβ) 40 and 42 concentrations in detergent-insoluble extracts of parieto-temporal cortex homogenates from 3xTg-AD mice. Low n-3:n-6 PUFA intake ratio increased insoluble tau regardless of total fat consumption, whereas high-fat diet incorporating a low n-3:n-6 PUFA ratio also increased soluble tau compared to controls. Moreover, the high-fat diet decreased cortical levels of the postsynaptic marker drebrin, while leaving presynaptic proteins synaptophysin, SNAP-25 and syntaxin 3 unchanged. Overall, these results suggest that high-fat consumption combined with low n-3 PUFA intake promote AD-like neuropathology.