Special lipid-based diets alleviate cognitive deficits in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease independent of brain amyloid deposition.
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.
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Hennariikka
H
Koivisto
Experimental Neurology, Saarland University, Homburg/Saar 66123, Germany; Deutsches Institut für Demenz Prävention, Saarland University, Homburg/Saar 66421, Germany.
Marcus O
MO
Grimm
Experimental Neurology, Saarland University, Homburg/Saar 66123, Germany.
Tatjana L
TL
Rothhaar
Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.
Róbert
R
Berkecz
Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn 53113, Germany.
Dieter
D
Lütjohann D
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Rajsa
R
Giniatullina
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Mari
M
Takalo
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Pasi O
PO
Miettinen
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Hanna-Maija
HM
Lahtinen
A. I. Virtanen Institute, University of Eastern Finland, Kuopio FI-70211, Finland.
Rashid
R
Giniatullin
Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.
Botond
B
Penke
Department Medical Chemistry, University of Szeged, Szeged 6720, Hungary.
Tamás
T
Janáky
Danone Research Centre for Specialised Nutrition, Wageningen 6700 CA, The Netherlands.
Laus M
LM
Broersen
Deutsches Institut für Demenz Prävention, Saarland University, Homburg/Saar 66421, Germany.
Tobias
T
Hartmann
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.
Heikki
H
Tanila
D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003072:Cognition Disorders / Q000188:drug therapy*; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic
D000682:Amyloid; D004041:Dietary Fats
APP processing; Amyloid-β; Fortasyn; Memory; Nutrition; Olfaction; Omega-3 fatty acid; Phospholipid; Phytosterol