title: Specialized Pro-Resolving Mediators from Omega-3 Fatty Acids Improve Amyloid-β Phagocytosis and Regulate Inflammation in Patients with Minor Cognitive Impairment.
abstract: In this review we discuss the immunopathology of Alzheimer's disease (AD) and recent advances in the prevention of minor cognitive impairment (MCI) by nutritional supplementation with omega-3 fatty acids. Defective phagocytosis of amyloid-β (Aβ) and abnormal inflammatory activation of peripheral blood mononuclear cells (PBMCs) are the two key immune pathologies of MCI and AD patients. The phagocytosis of Aβ by PBMCs of MCI and AD patients is universally defective and the inflammatory gene transcription is heterogeneously deregulated in comparison to normal subjects. Recent studies have discovered a cornucopia of beneficial anti-inflammatory and pro-resolving effects of the specialized proresolving mediators (SPMs) resolvins, protectins, maresins, and their metabolic precursors. Resolvin D1 and other mediators switch macrophages from an inflammatory to a tissue protective/pro-resolving phenotype and increase phagocytosis of Aβ. In a recent study of AD and MCI patients, nutritional supplementation by omega-3 fatty acids individually increased resolvin D1, improved Aβ phagocytosis, and regulated inflammatory genes toward a physiological state, but only in MCI patients. Our studies are beginning to dissect positive factors (adherence to Mediterranean diet with omega-3 and exercise) and negative factors (high fat diet, infections, cancer, and surgeries) in each patient. The in vitro and in vivo effects of omega-3 fatty acids and SPMs suggest that defective phagocytosis and chronic inflammation are related to defective production and/or defective signaling by SPMs in immune cells.
authors.affiliation: Department of Surgery, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Fiala
authors.affiliation: Departments of Anesthesiology, Basic Science Division, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Niccolo
authors.initials: N
authors.lastname: Terrando
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000276:immunology; D000818:Animals; D060825:Cognitive Dysfunction / Q000178:diet therapy* / Q000276:immunology*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006801:Humans
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Amyloid-β; fatty acids; inflammation; mild cognitive impairment; omega-3