A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model

By Giselle P. Lim, F. Calon, T. Morihara, Fusheng Yang, B. Teter, O. Ubeda, N. Salem, S. Frautschy, G. Cole. Journal of Neuroscience, 2005

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Epidemiological studies suggest that increased intake of the omega-3 (n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimer's disease (AD). DHA levels are lower in serum and brains of AD patients, which could result from low dietary intake and/or PUFA oxidation. Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. Aged animals (17-19 months old) were placed in one of three groups until 22.5 months of age: control (0.09% DHA), low-DHA (0%), or high-DHA (0.6%) chow. β-Amyloid (Aβ) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total Aβ by >70% when compared with low-DHA or control chow diets. Dietary DHA also decreased Aβ42 levels below those seen with control chow. Image analysis of brain sections with an antibody against Aβ (amino acids 1-13) revealed that overall plaque burden was significantly reduced by 40.3%, with the largest reductions (40-50%) in the hippocampus and parietal cortex. DHA modulated APP processing by decreasing both α- and β-APP C-terminal fragment products and full-length APP. BACE1 (β-secretase activity of the β-site APP-cleaving enzyme), ApoE (apolipoprotein E), and transthyretin gene expression were unchanged with the high-DHA diet. Together, these results suggest that dietary DHA could be protective against β-amyloid production, accumulation, and potential downstream toxicity.

Subfields: Molecular Biology, Nutrition and Dietetics, Surgery

View Paper: https://www.semanticscholar.org/paper/506319c4e97d99fb70341eff0ad415a20a848655

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Citations in the corpus

• Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids (2012, neutral): “[149–151].”
• A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. (2005, background): “org Volume 115 Number 10 October 2005 be achieved by decreasing γ-secretase activation, by decreasing antioxidative defenses, or both (22, 46).”
• MIND diet slows cognitive decline with aging (2015, background): “Fish are a rich source of long-chain n-3 fatty acids which have been shown to reduce Ab formation and oxidative damage and to increase synaptic proteins and dendritic spine density [47,48].”
• Omega-3 fatty acids EPA and DHA: health benefits throughout life. (2012, background): “The largest reductions (40–50%) were seen in brain regions that are thought to be involved with AD, the hippocampus and parietal cortex (51).”
• Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. (2006, neutral): “(%) Donepezil 33 (37) 33 (39) 10 (71) 11 (69) Galantamine 18 (20) 21 (25) 3 (21) 3 (19) Rivastigmine 38 (43) 31 (36) 1 (7) 2 (13) Acetylsalicylic acid 21 (24) 18 (21) 5 (36) 4 (25) Antidepressant agents 40 (45) 32 (38) 6 (43) 4 (25) Neuroleptic agents 9 (10) 5 (6) 1 (7) 0 Statin drugs 11 (12) 14 (16”