Omega-3 fatty acids increase OXPHOS energy for immune therapy of Alzheimer disease patients.

Sporadic late-onset Alzheimer disease (LOAD) preceded by mild cognitive impairment (MCI) is the most common type of dementia. Long-term studies of immunity to pathogenic amyloid-beta (A beta) in LOAD are lacking. Innate immunity of LOAD patients is malfunctioning in phagocytosis and degradation of A beta and LOAD patients' macrophage transcriptome and metabolome are deregulated. We previously showed omega-3 fatty acid (omega-3)-mediated repair of unfolded protein response and here we show much broader transcriptomic effects. omega-3 treatment in vitro and omega-3 supplementation by the drink Smartfish (SMF) in vivo increased the transcripts of the genes and pathways of immunity, glycolysis, tricarboxylic acid cycle, OX-PHOS, nicotinamide dinucleotide (NAD(+)) synthesis, and reversed the defects in A beta phagocytosis. In both peripheral blood mononuclear cells (PBMC) and macrophages, omega-3 increased ATP-linked oxygen consumption rate (OCR) and omega-3 with carnitine was superior to omega-3. omega-3 treatment in vitro and supplementation by the omega-3 drink SMF in vivo rescued macrophage phagocytosis when glycolysis or glycosylation were blocked. omega-3 provide flexible energy for immune clearance of the brain throughout the diurnal cycle, even in hypo- or hyper-glycemia. In certain LOAD patients, omega-3 may delay progression to dementia.