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Neurobiol Dis. 2015 Oct;82:552-60. doi: 10.1016/j.nbd.2015.09.002. Epub 2015 Sep 12.

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

Author information

  • 1Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA. Electronic address: eteng@ucla.edu.
  • 2Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • 3Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
  • 4Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Department of Neurobiology and Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • 5Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA; Biochemistry Department and Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
  • 6Retina Foundation of the Southwest, Dallas, TX, USA.
  • 7Retina Foundation of the Southwest, Dallas, TX, USA; Department of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, USA.

Abstract

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.

KEYWORDS:

Aggregation; Alzheimer's disease; Docosahexaenoic acid; Fibrillar; Hippocampus; Oligomers; Prefibrillar; Transgenic; β-amyloid

PMID:
26369878
PMCID:
PMC4641021
DOI:
10.1016/j.nbd.2015.09.002
[PubMed - indexed for MEDLINE]
Free PMC Article
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