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Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model


Year of Publication:
Contact PI Name:
Greg M. Cole
Contact PI Affiliation:
Department of Medicine, Department of Neurology University of California, Los Angeles, California, USA
Frédéric Calon, Giselle P. Lim, Fusheng Yang, Takashi Morihara, Bruce Teter, Oliver Ubeda, Phillippe Rostaing, Antoine Triller, Norman Salem Jr., Karen H. Ashe, Sally A. Frautschy
Primary Reference (PubMED ID):
Funding Source:
Veterans Affairs Office of Research and Development
National Institute on Aging (NIA)
Study Goal and Principal Findings:

This study investigated  effects of docosahexaenoic acid (DHA) on synaptic plasticity in Tg2576 mice. Epidemiological studies suggest that people who ingest higher levels of DHA are less likely to develop AD dementia. The reasons for the impact of DHA on learning and memory and the association with AD have been unclear but could result from its loss in synapses. Moreover, memory loss correlates better with synapse loss than with plaques or tangles. This study reported that reduction of dietary n-3 PFA in Tg2576 mice resulted in 80%– 90% losses of the p85α subunit of phosphatidylinositol 3-kinase and the postsynaptic actin-regulating protein drebrin. The loss of postsynaptic proteins was associated with increased oxidation, without concomitant neuron or presynaptic protein loss. N-3 PFA depletion increased caspase-cleaved actin, which was localized in dendrites ultrastructurally. Treatment of n-3 PFA restricted mice with DHA protected against these effects and behavioral deficits and increased antiapoptotic BAD phosphorylation. Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for AD.

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:
Not Reported

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
Hidden Platform Task
Synaptic Degeneration
Neuronal Loss
Caspase Activation
Postsynaptic Density Protein 95 (PSD95)
p85/Phosphoinositide 3-Kinase Regulatory Subunit 1 (PI3KR1)
Polyunsaturated Fatty Acid (PUFA)
Protein Oxidation
phospho-BCL2 Associated Agonist of Cell Death Protein (phospho-BAD)
Neuronal Loss