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Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice

Bibliographic

Year of Publication:
2006
Contact PI Name:
Heikki Tanila
Contact PI Affiliation:
Department of Neurobiology, A.I.Virtanen Institute, Univ. Kuopio, Neulaniementie, Kuopio, Finland
Co-Authors:
M. Oksman, H. Iivonen, E. Hogyes, Z. Amtul, B. Penke, I. Leenders, L. Broersen, D. Lutjohann, T. Hartmann
Primary Reference (PubMED ID):
Funding Source:
Finnish Neurology Foundation
German Federal Ministry of Education and Research (BMBF)
Humboldt Foundation
European Union Fifth Framework Project Fund
Study Goal and Principal Findings:

The present study assessed the influence of dietary lipids on accumulation of amyloid beta-peptide (Abeta) in the brain. Seven experimental diets with varying n-6/n-3-ratio, saturated and polyunsaturated fatty acid and cholesterol contents were fed to transgenic APPswe/PS1dE9 mice for 3-4 months beginning at a young adult age (6 months). Hippocampal Abeta levels were determined with ELISA and plaque load by using immunocytochemistry. A typical Western diet with 40% saturated fatty acids and 1% of cholesterol increased, while diets supplemented with docosahexaenoic acid (DHA) decreased Abeta levels compared to regular (soy oil based) diet. DHA diet also decreased the number of activated microglia in hippocampus and increased exploratory activity of transgenic mice, but did not improve their spatial learning in the water maze. The favorable effect of DHA on Abeta production was verified in two different cell lines. Regulation of dietary lipid intake may offer a new tool to reduce the risk of Alzheimer's disease at the population level.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Soy Oil-Based Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Corn Oil-Based Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Experimental Fish Oil-Based Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Standard Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Lipid Neutral Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Typical Western Diet
Therapeutic Target:
Multi Target
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Docosahexaenoic Acid (DHA)-Enriched Diet
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL6/J

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Morris Water Maze
Exploratory Activity
Histopathology
beta Amyloid Deposits
beta Amyloid Load
Activated Microglia
Congophillic Amyloid Deposits
Dense-core/Compact Plaques
Biochemical
Brain-beta Amyloid Peptide-Total
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Serum-Total Cholesterol
Saturated Fatty Acids (SFA)
Polyunsaturated Fatty Acid (PUFA)
Brain-Docosahexaenoic Acid (DHA)
Brain-Eicosapentaenoic Acid (EPA)
Omega-6 Fatty Acid Levels
Omega-3 Fatty Acid Levels
Monosaturated Fatty Acid Levels
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
CD45
Immunochemistry
CD45
beta Amyloid Load
Brain-beta Amyloid Deposits
Cell Biology
beta Amyloid Peptides
Pharmacokinetics
Blood Brain Barrier Penetration
Toxicology
Body Weight