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Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition.

Abstract

Dietary fish oil, providing n3 polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), associates with reduced dementia risk in epidemiological studies and reduced amyloid accumulation in Alzheimer mouse models. We now studied whether additional nutrients can improve the efficacy of fish oil in alleviating cognitive deficits and amyloid pathology in APPswe/PS1dE9 transgenic and wild-type mice. We compared four isocaloric (5% fat) diets. The fish oil diet differed from the control diet only by substituted fish oil. Besides fish oil, the plant sterol diet was supplemented with phytosterols, while the Fortasyn diet contained as supplements precursors and cofactors for membrane synthesis, viz. uridine-monophosphate; DHA and EPA; choline; folate; vitamins B6, B12, C and E; phospholipids and selenium. Mice began the special diets at 5 months and were sacrificed at 14 months after behavioral testing. Transgenic mice, fed with control chow, showed poor spatial learning, hyperactivity in exploring a novel cage and reduced preference to explore novel odors. All fish-oil-containing diets increased exploration of a novel odor over a familiar one. Only the Fortasyn diet alleviated the spatial learning deficit. None of the diets influenced hyperactivity in a new environment. Fish-oil-containing diets strongly inhibited β- and γ-secretase activity, and the plant sterol diet additionally reduced amyloid-β 1-42 levels. These data indicate that beneficial effects of fish oil on cognition in Alzheimer model mice can be enhanced by adding other specific nutrients, but this effect is not necessarily mediated via reduction of amyloid accumulation.

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  • Authors+Show Affiliations

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    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

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    Experimental Neurology, Saarland University, Homburg/Saar 66123, Germany; Deutsches Institut für Demenz Prävention, Saarland University, Homburg/Saar 66421, Germany.

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    Experimental Neurology, Saarland University, Homburg/Saar 66123, Germany.

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    Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.

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    Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn 53113, Germany.

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    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

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    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

    ,

    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

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    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

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    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.

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    Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.

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    Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.

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    Danone Research Centre for Specialised Nutrition, Wageningen 6700 CA, The Netherlands.

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    Deutsches Institut für Demenz Prävention, Saarland University, Homburg/Saar 66421, Germany.

    A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland; Department of Neurology, Kuopio University Hospital, Kuopio FI-70211, Finland. Electronic address: Heikki.Tanila@uef.fi.

    Source

    MeSH

    Alzheimer Disease
    Amyloid
    Animals
    Brain
    Chromatography, High Pressure Liquid
    Cognition Disorders
    Dietary Fats
    Disease Models, Animal
    Mice
    Mice, Transgenic

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24445040

    Citation

    Koivisto, Hennariikka, et al. "Special Lipid-based Diets Alleviate Cognitive Deficits in the APPswe/PS1dE9 Transgenic Mouse Model of Alzheimer's Disease Independent of Brain Amyloid Deposition." The Journal of Nutritional Biochemistry, vol. 25, no. 2, 2014, pp. 157-69.
    Koivisto H, Grimm MO, Rothhaar TL, et al. Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. J Nutr Biochem. 2014;25(2):157-69.
    Koivisto, H., Grimm, M. O., Rothhaar, T. L., Berkecz, R., Lütjohann D, D., Giniatullina, R., ... Tanila, H. (2014). Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. The Journal of Nutritional Biochemistry, 25(2), pp. 157-69. doi:10.1016/j.jnutbio.2013.09.015.
    Koivisto H, et al. Special Lipid-based Diets Alleviate Cognitive Deficits in the APPswe/PS1dE9 Transgenic Mouse Model of Alzheimer's Disease Independent of Brain Amyloid Deposition. J Nutr Biochem. 2014;25(2):157-69. PubMed PMID: 24445040.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. AU - Koivisto,Hennariikka, AU - Grimm,Marcus O, AU - Rothhaar,Tatjana L, AU - Berkecz,Róbert, AU - Lütjohann D,Dieter, AU - Giniatullina,Rajsa, AU - Takalo,Mari, AU - Miettinen,Pasi O, AU - Lahtinen,Hanna-Maija, AU - Giniatullin,Rashid, AU - Penke,Botond, AU - Janáky,Tamás, AU - Broersen,Laus M, AU - Hartmann,Tobias, AU - Tanila,Heikki, Y1 - 2013/11/06/ PY - 2013/04/24/received PY - 2013/08/30/revised PY - 2013/09/11/accepted PY - 2014/1/22/entrez PY - 2014/1/22/pubmed PY - 2014/9/16/medline KW - APP processing KW - Amyloid-β KW - Fortasyn KW - Memory KW - Nutrition KW - Olfaction KW - Omega-3 fatty acid KW - Phospholipid KW - Phytosterol SP - 157 EP - 69 JF - The Journal of nutritional biochemistry JO - J. Nutr. Biochem. VL - 25 IS - 2 N2 - Dietary fish oil, providing n3 polyunsaturated fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), associates with reduced dementia risk in epidemiological studies and reduced amyloid accumulation in Alzheimer mouse models. We now studied whether additional nutrients can improve the efficacy of fish oil in alleviating cognitive deficits and amyloid pathology in APPswe/PS1dE9 transgenic and wild-type mice. We compared four isocaloric (5% fat) diets. The fish oil diet differed from the control diet only by substituted fish oil. Besides fish oil, the plant sterol diet was supplemented with phytosterols, while the Fortasyn diet contained as supplements precursors and cofactors for membrane synthesis, viz. uridine-monophosphate; DHA and EPA; choline; folate; vitamins B6, B12, C and E; phospholipids and selenium. Mice began the special diets at 5 months and were sacrificed at 14 months after behavioral testing. Transgenic mice, fed with control chow, showed poor spatial learning, hyperactivity in exploring a novel cage and reduced preference to explore novel odors. All fish-oil-containing diets increased exploration of a novel odor over a familiar one. Only the Fortasyn diet alleviated the spatial learning deficit. None of the diets influenced hyperactivity in a new environment. Fish-oil-containing diets strongly inhibited β- and γ-secretase activity, and the plant sterol diet additionally reduced amyloid-β 1-42 levels. These data indicate that beneficial effects of fish oil on cognition in Alzheimer model mice can be enhanced by adding other specific nutrients, but this effect is not necessarily mediated via reduction of amyloid accumulation. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/24445040/Special_lipid_based_diets_alleviate_cognitive_deficits_in_the_APPswe/PS1dE9_transgenic_mouse_model_of_Alzheimer's_disease_independent_of_brain_amyloid_deposition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0955-2863(13)00225-8 DB - PRIME DP - Unbound Medicine ER -