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A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model.
J Neurosci 2005; 25(12):3032-40JN

Abstract

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. beta-Amyloid (Abeta) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total Abeta by >70% when compared with low-DHA or control chow diets. Dietary DHA also decreased Abeta42 levels below those seen with control chow. Image analysis of brain sections with an antibody against Abeta (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 alpha- and beta-APP C-terminal fragment products and full-length APP. BACE1 (beta-secretase activity of the beta-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 beta-amyloid production, accumulation, and potential downstream toxicity.

Authors+Show Affiliations

Department of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15788759

Citation

Lim, Giselle P., et al. "A Diet Enriched With the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 25, no. 12, 2005, pp. 3032-40.
Lim GP, Calon F, Morihara T, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005;25(12):3032-40.
Lim, G. P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., ... Cole, G. M. (2005). A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 25(12), pp. 3032-40.
Lim GP, et al. A Diet Enriched With the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model. J Neurosci. 2005 Mar 23;25(12):3032-40. PubMed PMID: 15788759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. AU - Lim,Giselle P, AU - Calon,Frédéric, AU - Morihara,Takashi, AU - Yang,Fusheng, AU - Teter,Bruce, AU - Ubeda,Oliver, AU - Salem,Norman,Jr AU - Frautschy,Sally A, AU - Cole,Greg M, PY - 2005/3/25/pubmed PY - 2006/3/15/medline PY - 2005/3/25/entrez SP - 3032 EP - 40 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 25 IS - 12 N2 - 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. beta-Amyloid (Abeta) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total Abeta by >70% when compared with low-DHA or control chow diets. Dietary DHA also decreased Abeta42 levels below those seen with control chow. Image analysis of brain sections with an antibody against Abeta (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 alpha- and beta-APP C-terminal fragment products and full-length APP. BACE1 (beta-secretase activity of the beta-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 beta-amyloid production, accumulation, and potential downstream toxicity. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/15788759/A_diet_enriched_with_the_omega_3_fatty_acid_docosahexaenoic_acid_reduces_amyloid_burden_in_an_aged_Alzheimer_mouse_model_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=15788759 DB - PRIME DP - Unbound Medicine ER -