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FASEB J. 2017 Aug;31(8):3229-3239. doi: 10.1096/fj.201700065R. Epub 2017 Apr 18.

Modulation of innate immunity of patients with Alzheimer's disease by omega-3 fatty acids.

Author information

1
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA; mfiala@ucla.edu.
2
Department of Molecular Cell Biology and Immunology, Vrije Universiteit (VU) Medical Center, Multiple Sclerosis Center Amsterdam, Amsterdam, The Netherlands.
3
Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Entomology, University of California, Davis, Davis, California, USA.
5
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.

Abstract

The innate immune system of patients with Alzheimer's disease and mild cognitive impairment (MCI) is deregulated with highly increased or decreased transcription of inflammatory genes and consistently depressed phagocytosis of amyloid-β1-42 (Aβ) by monocytes and macrophages. Current immune therapies target single mechanisms in the adaptive immune system but not innate immunity. Here, we summarize recent advances in therapy by ω-3, ω-6, and epoxy fatty acids; specialized proresolving mediators; and vitamin D3 that have proven immune effects and emerging cognitive effects in patients with MCI. The hypothesis of this approach is that macrophages of normal participants, but not those of patients with Alzheimer's disease and MCI, possess effective phagocytosis for Aβ and protect homeostasis of the brain and, furthermore, that defective MCI macrophages recover phagocytic function via ω-3. Recent studies of fish-derived ω-3 supplementation in patients with MCI have shown polarization of Apoε3/ε3 patients' macrophages to an intermediate M1-M2 phenotype that is optimal for Aβ phagocytosis and the stabilization of cognitive decline. Therefore, accumulating preclinical and preliminary clinical evidence indicates that ω-3 supplementation should be tested in a randomized controlled clinical trial and that the analysis should involve the apolipoprotein E genotype and intervening conditions during trial.-Fiala, M., Kooij, G., Wagner, K., Hammock, B., Pellegrini, M. Modulation of innate immunity of patients with Alzheimer's disease by omega-3 fatty acids.

PMID:
28420693
PMCID:
PMC5503712
DOI:
10.1096/fj.201700065R
[Indexed for MEDLINE]
Free PMC Article

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