A diet high in omega-3 fatty acids does not improve or protect cognitive performance in Alzheimer's transgenic mice



Year of Publication:
Contact PI Name:
Gary W. Arendash
Contact PI Affiliation:
The Byrd Alzheimer’s Institute, Tampa, Florida, USA
M.T. Jensen, N. Salem Jr., N. Hussein, J. Cracchiolo, A. Dickson, R. Leighty, H. Potter
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
Study Goal and Principal Findings:

Although a number of epidemiologic studies reported that higher intake of omega-3 fatty acids (largely associated with fish consumption) is protective against Alzheimer’s disease (AD), other human studies reported no such effect. Because retrospective human studies are problematic and controlled longitudinal studies over decades are impractical, the present study utilized Alzheimer’s transgenic mice (Tg) in a highly controlled study to determine whether a diet high in omega-3 fatty acid, equivalent to the 13% omega-3 fatty acid diet of Greenland Eskimos, can improve cognitive performance or protect against cognitive impairment. Amyloid precursor protein (APP)-swPS1 double transgenic mice, as well as nontransgenic (NT) normal littermates, were given a high omega-3 supplemented diet or a standard diet from 2 through 9 months of age, with a comprehensive behavioral test battery administered during the final 6 weeks. For both Tg and NT mice, long-term n-3 supplementation resulted in cognitive performance that was no better than that of mice fed a standard diet. In NT mice, the high omega-3 diet increased cortical levels of omega-3 fatty acids while decreasing omega-6 levels. However, the high omega-3 diet had no effect on cortical fatty acid levels in Tg mice. Irrespective of diet, no correlations existed between brain omega-3 levels and cognitive performance for individual NT or Tg mice. In contrast, brain levels of omega-6 fatty acids were strongly correlated with cognitive impairment for both genotypes. Thus, elevated brain levels of omega-3 fatty acids were not relevant to cognitive function, whereas high brain levels of omega-6 were associated with impaired cognitive function. In Tg mice, the omega-3 supplemental diet did not induce significant changes in soluble/insoluble Aβ within the hippocampus, although strong correlations were evident between hippocampal Aβ1– 40 levels and cognitive impairment. While these studies involved a genetically manipulated mouse model of AD, the results suggest that diets high in omega-3 fatty acids, or use of fish oil supplements (DHA EPA), will not protect against AD, at least in high-risk individuals. However, normal individuals conceivably could derive cognitive benefits from high omega-3 intake if it corrects an elevation in the brain level of n-6 fatty acids as a result. Alternatively, dietary fish may contain nutrients, other than DHA and EPA, that could provide some protection against AD. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Omega-3 Fatty Acid
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:
C57/B6/SJL/Swiss Webster

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
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


Outcome Measured
Outcome Parameters
Open Field Test
Y Maze
Elevated Plus Maze
Morris Water Maze
Circular Platform
Platform Recognition
Radial Arm Water Maze
Motor Function
Balance Beam Test
String Agility Test
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Saturated Fatty Acids (SFA)
Monosaturated Fatty Acid Levels
Omega-6 Fatty Acid Levels
Omega-3 Fatty Acid Levels
Body Weight

Source URL: http://alzped.nia.nih.gov/diet-high-omega-3-fatty-acids