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

Hennariikka Koivisto, Marcus O. Grimm, Tatjana L. Rothhaar, Róbert Berkecz, Dieter Lütjohann D, Rajsa Giniatullina, Mari Takalo, Pasi O. Miettinen, Hanna Maija Lahtinen, Rashid Giniatullin, Botond Penke, Tamás Janáky, Laus M. Broersen, Tobias Hartmann, Heikki Tanila

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)157-169
Number of pages13
JournalJournal of Nutritional Biochemistry
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 1 2014

Keywords

  • APP processing
  • Amyloid-β
  • Fortasyn
  • Memory
  • Nutrition
  • Olfaction
  • Omega-3 fatty acid
  • Phospholipid
  • Phytosterol

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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    Koivisto, H., Grimm, M. O., Rothhaar, T. L., Berkecz, R., Lütjohann D, D., Giniatullina, R., Takalo, M., Miettinen, P. O., Lahtinen, H. M., Giniatullin, R., Penke, B., Janáky, T., Broersen, L. M., Hartmann, T., & 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. Journal of Nutritional Biochemistry, 25(2), 157-169. https://doi.org/10.1016/j.jnutbio.2013.09.015