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A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice.

Abstract

Although a number of epidemiologic studies reported that higher intake of omega-3 fatty acids (largely associated with fish consumption) is protective against Alzheimer's disease (AD), other human studies reported no such effect. Because retrospective human studies are problematic and controlled longitudinal studies over decades are impractical, the present study utilized Alzheimer's transgenic mice (Tg) in a highly controlled study to determine whether a diet high in omega-3 fatty acid, equivalent to the 13% omega-3 fatty acid diet of Greenland Eskimos, can improve cognitive performance or protect against cognitive impairment. Amyloid precursor protein (APP)-sw+PS1 double transgenic mice, as well as nontransgenic (NT) normal littermates, were given a high omega-3 supplemented diet or a standard diet from 2 through 9 months of age, with a comprehensive behavioral test battery administered during the final 6 weeks. For both Tg and NT mice, long-term n-3 supplementation resulted in cognitive performance that was no better than that of mice fed a standard diet. In NT mice, the high omega-3 diet increased cortical levels of omega-3 fatty acids while decreasing omega-6 levels. However, the high omega-3 diet had no effect on cortical fatty acid levels in Tg mice. Irrespective of diet, no correlations existed between brain omega-3 levels and cognitive performance for individual NT or Tg mice. In contrast, brain levels of omega-6 fatty acids were strongly correlated with cognitive impairment for both genotypes. Thus, elevated brain levels of omega-3 fatty acids were not relevant to cognitive function, whereas high brain levels of omega-6 were associated with impaired cognitive function. In Tg mice, the omega-3 supplemental diet did not induce significant changes in soluble/insoluble Abeta within the hippocampus, although strong correlations were evident between hippocampal Abeta(1-40) levels and cognitive impairment. While these studies involved a genetically manipulated mouse model of AD, our results suggest that diets high in omega-3 fatty acids, or use of fish oil supplements (DHA+EPA), will not protect against AD, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of n-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, that could provide some protection against AD.

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  • Authors+Show Affiliations

    ,

    The Florida Alzheimer's Disease Research Center and The Byrd Alzheimer's Institute, Tampa, FL 33613, USA. arendash@cas.usf.edu

    , , , , , ,

    Source

    Neuroscience 149:2 2007 Oct 26 pg 286-302

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Animals
    Anxiety
    Chromatography, Gas
    Cognition
    Cognition Disorders
    Diet
    Enzyme-Linked Immunosorbent Assay
    Exploratory Behavior
    Fatty Acids, Omega-3
    Hippocampus
    Humans
    Maze Learning
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Nerve Tissue Proteins
    Postural Balance
    Presenilin-1
    Psychomotor Performance
    Recognition (Psychology)

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17904756

    Citation

    Arendash, G W., et al. "A Diet High in Omega-3 Fatty Acids Does Not Improve or Protect Cognitive Performance in Alzheimer's Transgenic Mice." Neuroscience, vol. 149, no. 2, 2007, pp. 286-302.
    Arendash GW, Jensen MT, Salem N, et al. A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice. Neuroscience. 2007;149(2):286-302.
    Arendash, G. W., Jensen, M. T., Salem, N., Hussein, N., Cracchiolo, J., Dickson, A., ... Potter, H. (2007). A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice. Neuroscience, 149(2), pp. 286-302.
    Arendash GW, et al. A Diet High in Omega-3 Fatty Acids Does Not Improve or Protect Cognitive Performance in Alzheimer's Transgenic Mice. Neuroscience. 2007 Oct 26;149(2):286-302. PubMed PMID: 17904756.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice. AU - Arendash,G W, AU - Jensen,M T, AU - Salem,N,Jr AU - Hussein,N, AU - Cracchiolo,J, AU - Dickson,A, AU - Leighty,R, AU - Potter,H, Y1 - 2007/08/14/ PY - 2007/03/12/received PY - 2007/07/17/revised PY - 2007/08/04/accepted PY - 2007/10/2/pubmed PY - 2008/1/17/medline PY - 2007/10/2/entrez SP - 286 EP - 302 JF - Neuroscience JO - Neuroscience VL - 149 IS - 2 N2 - Although a number of epidemiologic studies reported that higher intake of omega-3 fatty acids (largely associated with fish consumption) is protective against Alzheimer's disease (AD), other human studies reported no such effect. Because retrospective human studies are problematic and controlled longitudinal studies over decades are impractical, the present study utilized Alzheimer's transgenic mice (Tg) in a highly controlled study to determine whether a diet high in omega-3 fatty acid, equivalent to the 13% omega-3 fatty acid diet of Greenland Eskimos, can improve cognitive performance or protect against cognitive impairment. Amyloid precursor protein (APP)-sw+PS1 double transgenic mice, as well as nontransgenic (NT) normal littermates, were given a high omega-3 supplemented diet or a standard diet from 2 through 9 months of age, with a comprehensive behavioral test battery administered during the final 6 weeks. For both Tg and NT mice, long-term n-3 supplementation resulted in cognitive performance that was no better than that of mice fed a standard diet. In NT mice, the high omega-3 diet increased cortical levels of omega-3 fatty acids while decreasing omega-6 levels. However, the high omega-3 diet had no effect on cortical fatty acid levels in Tg mice. Irrespective of diet, no correlations existed between brain omega-3 levels and cognitive performance for individual NT or Tg mice. In contrast, brain levels of omega-6 fatty acids were strongly correlated with cognitive impairment for both genotypes. Thus, elevated brain levels of omega-3 fatty acids were not relevant to cognitive function, whereas high brain levels of omega-6 were associated with impaired cognitive function. In Tg mice, the omega-3 supplemental diet did not induce significant changes in soluble/insoluble Abeta within the hippocampus, although strong correlations were evident between hippocampal Abeta(1-40) levels and cognitive impairment. While these studies involved a genetically manipulated mouse model of AD, our results suggest that diets high in omega-3 fatty acids, or use of fish oil supplements (DHA+EPA), will not protect against AD, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of n-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, that could provide some protection against AD. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17904756/A_diet_high_in_omega_3_fatty_acids_does_not_improve_or_protect_cognitive_performance_in_Alzheimer's_transgenic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(07)00994-3 DB - PRIME DP - Unbound Medicine ER -