Resolution of inflammation is altered in Alzheimer's disease

• Published in: Alzheimer's & dementia Vol. 11; no. 1; pp. 40 - 50.e2
• Main Authors: Wang, Xiuzhe, Zhu, Mingqin, Hjorth, Erik, Cortés-Toro, Veronica, Eyjolfsdottir, Helga, Graff, Caroline, Nennesmo, Inger, Palmblad, Jan, Eriksdotter, Maria, Sambamurti, Kumar, Fitzgerald, Jonathan M, Serhan, Charles N, Granholm, Ann-Charlotte, Schultzberg, Marianne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2015
• Subjects: 15-Lipoxygenase-2; Aged; ALX/FPR2; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - enzymology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Case-Control Studies; ChemR23; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - enzymology; Cognitive Dysfunction - pathology; Docosahexaenoic Acids - cerebrospinal fluid; ELISA; Female; FPRL1; Hippocampus - enzymology; Hippocampus - metabolism; Hippocampus - pathology; Human; Humans; Immunohistochemistry; Inflammation - cerebrospinal fluid; Inflammation - enzymology; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - cerebrospinal fluid; Inflammation Mediators - metabolism; Lipoxin A4; Lipoxins - cerebrospinal fluid; Lipoxygenase - cerebrospinal fluid; Male; Middle Aged; Mild cognitive impairment; Neurology; Receptors, Formyl Peptide - analysis; Receptors, Lipoxin - analysis; Resolvin D1; Specialized pro-resolving mediators; Tau; tau Proteins - cerebrospinal fluid; Human; Immunohistochemistry; Mild cognitive impairment; Tau; Lipoxin A 4; ALX/FPR2; 15-Lipoxygenase-2; ChemR23; FPRL1; Resolvin D1; ELISA; Specialized pro-resolving mediators; Lipoxin A4; Lipoxin A
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1016/j.jalz.2013.12.024

Abstract Background Resolution is the final stage of the inflammatory response, when restoration of tissue occurs. Failure may lead to chronic inflammation, which is known as part of the pathology in the brain of individuals with Alzheimer's disease (AD). Methods Specialized pro-resolving mediators (SPMs), receptors, biosynthetic enzyme, and downstream effectors involved in resolution were analyzed in postmortem hippocampal tissue from AD patients and non-AD subjects. SPMs were analyzed in cerebrospinal fluid (CSF). Results SPMs and SPM receptors were detected in the human brain. Levels of the SPM lipoxin A4 (LXA4 ) were reduced in AD, both in the CSF and hippocampus. An enzyme involved in LXA4 synthesis and two SPM receptors were elevated in AD brains. LXA4 and RvD1 levels in CSF correlated with Mini-Mental State Examination (MMSE) scores. Conclusions A resolution pathway exists in the brain and the alterations described herein strongly suggest a dysfunction of this pathway in AD. MMSE correlations suggest a connection with cognitive function in AD.