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P2‐001: MITOCHONDRIAL ENERGY FROM OMEGA‐3 FOR AMYLOID‐BETA PHAGOCYTOSIS
Author(s) -
Fiala Milan,
Pellegrini Matteo A.,
Stiles Linsey
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4960
Subject(s) - phagocytosis , glycolysis , oxidative phosphorylation , biology , microbiology and biotechnology , biochemistry , metabolism
Background: The innate immune system clears amyloid-b (Ab) by phagocytosis but is failing in Mild cognitive impairment patients (MCI) (reversibly) and in Alzheimer disease patients (AD) (irreversibly). Omega-3 fatty acids (omega-3), vitamin 1,25D3, and curcuminoids mend AD patients’ phagocytic and transcriptional defects. Supplementation by a fish-derived lipid emulsion with omega-3 Smartfish (SMF) (Oslo, Norway) recovered Ab phagocytosis and was associated with 2.2 point increase/year in the MiniMental State Exam (MMSE) score in APOEe3/e3 and no change in APOEe3/e4 MCI. Here, we investigate the effect of omega-3 supplementation on mitochondrial respiration and glycolysis in immune cells of MCI.Methods: Wemeasured Ab phagocytosis by the flow cytometric test with peripheral blood mononuclear cells (PBMC) using fluorescent Ab. We performed RNA-seq of macrophages using Illumina HiSeq 4000, aligned reads to the UCSC hg19 reference genome and obtained read counts using HT-Seq. We analyzed mitochondrial function in PBMC by the Seahorse technique and used the inhibitors of oxidative phosphorylation and glycolysis to analyze by ANOVA the role of electron transport chain components and glycolysis in Ab phagocytosis. Results: Omega-3 treatment of macrophages in vitro increased transcription of cytoprotective genes and decreased proapoptotic genes. Omega3 increased basal oxygen consumption rate (OCR), ATP-linked OCR, and OCAR/ECAR ratio, but not extracellular acidification rate (ECAR). In non-supplemented subjects, Ab phagocytosis was sensitive to an inhibition of a) Complex I by rotenone; b) mitochondrial pyruvate carrier byUK-5099; c) carnitine palmitoyltransferase by etomoxir; d) glycolysis by iodoacetate. Conclusions: Cell signaling and increased energy from a fish-derived emulsion of omega-3 recover the immune functions of MCI through increased mitochondrial energy and unfolded protein response. In individual patients, the changes in cognitive and immune status show parallel increases or decreases. Omega-3 supplementation of some SCI and MCI patients is associated with cognitive stabilization for 3 years, but has no effect on AD and Dementia with Lewy Bodies disease (DLB) patients.