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, R. Berkecz, Dieter Lütjohann D, Rajsa Giniatullina, Mari Takalo, Pasi O. Miettinen, Hanna Maija Lahtinen, Rashid Giniatullin, B. Penke, T. Janáky, Laus M. Broersen, Tobias Hartmann, Heikki Tanila

Research output: Contribution to journalArticle

28 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 2014

Fingerprint

Nutrition
Amyloid
Transgenic Mice
Fish Oils
Brain
Alzheimer Disease
Diet
Lipids
Phytosterols
Eicosapentaenoic Acid
Docosahexaenoic Acids
Odors
Nutrients
Unsaturated Dietary Fats
Uridine Monophosphate
Food
Amyloid Precursor Protein Secretases
Vitamin B 6
Omega-3 Fatty Acids
Pathology

Keywords

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

ASJC Scopus subject areas

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

Cite this

Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. / Koivisto, Hennariikka; Grimm, Marcus O.; Rothhaar, Tatjana L.; Berkecz, R.; Lütjohann D, Dieter; Giniatullina, Rajsa; Takalo, Mari; Miettinen, Pasi O.; Lahtinen, Hanna Maija; Giniatullin, Rashid; Penke, B.; Janáky, T.; Broersen, Laus M.; Hartmann, Tobias; Tanila, Heikki.

In: Journal of Nutritional Biochemistry, Vol. 25, No. 2, 02.2014, p. 157-169.

Research output: Contribution to journalArticle

Koivisto, H, Grimm, MO, Rothhaar, TL, Berkecz, R, Lütjohann D, D, Giniatullina, R, Takalo, M, Miettinen, PO, Lahtinen, HM, Giniatullin, R, Penke, B, Janáky, T, Broersen, LM, 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, vol. 25, no. 2, pp. 157-169. https://doi.org/10.1016/j.jnutbio.2013.09.015
Koivisto, Hennariikka ; Grimm, Marcus O. ; Rothhaar, Tatjana L. ; Berkecz, R. ; Lütjohann D, Dieter ; Giniatullina, Rajsa ; Takalo, Mari ; Miettinen, Pasi O. ; Lahtinen, Hanna Maija ; Giniatullin, Rashid ; Penke, B. ; Janáky, T. ; Broersen, Laus M. ; Hartmann, Tobias ; Tanila, Heikki. / Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition. In: Journal of Nutritional Biochemistry. 2014 ; Vol. 25, No. 2. pp. 157-169.
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