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Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization


Year of Publication:
Contact PI Name:
Edmond Teng
Contact PI Affiliation:
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, USA
Karen Taylor, Tina Bilousova, David Weiland, Thaidan Pham, Xiaohong Zuo, Fusheng Yang, Ping-Ping Chen, Charles G. Glabe, Alison Takac, Dennis R. Hoffman, Sally A. Frautschy, Gregory M. Cole
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
John A. Hartford Foundation
American Federation for Aging Research
Study Goal and Principal Findings:

Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on β-amyloid (Aβ) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Aβ oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Aβ indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Aβ plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Aβ oligomer levels in the hippocampus. Further quantification of specific conformational populations of Aβ oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Aβ oligomers and decreased prefibrillar (i.e. putatively more toxic) Aβ oligomers. These results provide in vivo evidence suggesting that DHA can modulate Aβ aggregation by stabilizing soluble fibrillar Aβ oligomers and thus reduce the formation of both Aβ plaques and prefibrillar Aβ oligomers. However, since fibrillar Aβ oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Aβ oligomer levels for more effective prevention of AD in clinical settings.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Dietary Interventions & Supplements
Therapeutic Agent:
Docosahexaenoic Acid (DHA)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Sprague Dawley

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
Morris Water Maze
Polyunsaturated Fatty Acid (PUFA)
CSF-beta Amyloid Peptide 42
Ionized Calcium Binding Adaptor Molecule 1 (Iba1)
Amyloid Precursor Protein (APP)
APP-CTF83 (CTF alpha)
APP-CTF99 (CTF beta)
Brain-beta Amyloid Oligomers
Brain-Guanidine Soluble beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 42
Brain-Soluble Amyloid Precursor Protein alpha (sAPP alpha)
beta Amyloid *56
Brain-beta Amyloid Fibrils
Glutamate Ionotropic Receptor NMDA Type Subunit 2B (GluN2B/NR2B)
beta Amyloid Load
CSF-beta Amyloid Peptide 42
Food Intake