title: Resolution of inflammation is altered in Alzheimer's disease.
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.
authors: Department of Neurobiology, Care Sciences and Society, Section of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors: Xiuzhe
authors: X
authors: Wang
authors: Department of Neurobiology, Care Sciences and Society, Section of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors: Mingqin
authors: M
authors: Zhu
authors: Department of Neurobiology, Care Sciences and Society, Section of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors: Erik
authors: E
authors: Hjorth
authors: Department of Neurobiology, Care Sciences and Society, Section of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
authors: Veronica
authors: V
authors: Cortés-Toro
authors: Department of Neurobiology, Care Sciences and Society, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
authors: Helga
authors: H
authors: Eyjolfsdottir
authors: Department of Neurobiology, Care Sciences and Society, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
authors: Caroline
authors: C
authors: Graff
authors: Department of Laboratory Medicine, Section of Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Inger
authors: I
authors: Nennesmo
authors: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Jan
authors: J
authors: Palmblad
authors: Department of Neurobiology, Care Sciences and Society, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
authors: Maria
authors: M
authors: Eriksdotter
authors: Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC, USA.
authors: Kumar
authors: K
authors: Sambamurti
authors: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Jonathan M
authors: JM
authors: Fitzgerald
authors: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors: Charles N
authors: CN
authors: Serhan
authors: Department of Neurosciences and the Center on Aging, Medical University of South Carolina, Charleston, SC, USA.
authors: Ann-Charlotte
authors: AC
authors: Granholm
authors: Department of Neurobiology, Care Sciences and Society, Section of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden. Electronic address: marianne.schultzberg@ki.se.
authors: Marianne
authors: M
authors: Schultzberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000473:pathology; D004281:Docosahexaenoic Acids / Q000134:cerebrospinal fluid; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid / Q000378:metabolism*; D044045:Lipoxins / Q000134:cerebrospinal fluid; D008084:Lipoxygenase / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D044042:Receptors, Formyl Peptide / Q000032:analysis; D044067:Receptors, Lipoxin / Q000032:analysis; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C105101:FPR2 protein, human; D018836:Inflammation Mediators; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4; C518399:resolvin D1; D016875:tau Proteins; D004281:Docosahexaenoic Acids; D008084:Lipoxygenase
keywords: 15-Lipoxygenase-2; ALX/FPR2; ChemR23; ELISA; FPRL1; Human; Immunohistochemistry; Lipoxin A(4); Mild cognitive impairment; Resolvin D1; Specialized pro-resolving mediators; Tau