1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients.

Authors: Mizwicki MT; Liu G; Fiala M; Magpantay L; Sayre J; Siani A; Mahanian M; Weitzman R; Hayden EY; Rosenthal MJ; Nemere I; Ringman J; Teplow DB

Abstract: As immune defects in amyloid-beta (Abeta) phagocytosis and degradation underlie Abeta deposition and inflammation in Alzheimer's disease (AD) brain, better understanding of the relation between Abeta phagocytosis and inflammation could lead to promising preventive strategies. We tested two immune modulators in peripheral blood mononuclear cells (PBMCs) of AD patients and controls: 1alpha,25(OH)2-vitamin D3 (1,25D3) and resolvin D1 (RvD1). Both 1,25D3 and RvD1 improved phagocytosis of FAM-Abeta by AD macrophages and inhibited fibrillar Abeta-induced apoptosis. The action of 1,25D3 depended on the nuclear vitamin D and the protein disulfide isomerase A3 receptors, whereas RvD1 required the chemokine receptor, GPR32. The activities of 1,25D3 and RvD1 commonly required intracellular calcium, MEK1/2, PKA, and PI3K signaling; however, the effect of RvD1 was more sensitive to pertussis toxin. In this case study, the AD patients: a) showed significant transcriptional up regulation of IL1RN, ITGB2, and NFkappaB; and b) revealed two distinct groups when compared to controls: group 1 decreased and group 2 increased transcription of TLRs, IL-1, IL1R1 and chemokines. In the PBMCs/macrophages of both groups, soluble Abeta (sAbeta) increased the transcription/secretion of cytokines (e.g., IL1 and IL6) and chemokines (e.g., CCLs and CXCLs) and 1,25D3/RvD1 reversed most of the sAbeta effects. However, they both further increased the expression of IL1 in the group 1, sbeta-treated cells. We conclude that in vitro, 1,25D3 and RvD1 rebalance inflammation to promote Abeta phagocytosis, and suggest that low vitamin D3 and docosahexaenoic acid intake and/or poor anabolic production of 1,25D3/RvD1 in PBMCs could contribute to AD onset/pathology.

Journal: Journal of Alzheimer's disease : JAD
Volume: 34
Issue: 1
Pages: 155-70
Date: Nov. 29, 2012
PMID: 23186989
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Notes:

[http://www.biocompare.com/life-science-news/130352-vitamin-d-omega-3-may-help-clear-amyloid-plaques-found-in-alzheimer-s/]



Categories: Alzheimer's Disease
Citation:

Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB (2013) 1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients. Journal of Alzheimer's disease : JAD 34: 155-70.



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