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Resolution of inflammation is altered in Alzheimer's disease
Author(s) -
Wang Xiuzhe,
Zhu Mingqin,
Hjorth Erik,
CortésToro Veronica,
Eyjolfsdottir Helga,
Graff Caroline,
Nennesmo Inger,
Palmblad Jan,
Eriksdotter Maria,
Sambamurti Kumar,
Fitzgerald Jonathan M.,
Serhan Charles N.,
Granholm AnnCharlotte,
Schultzberg Marianne
Publication year - 2015
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.2013.12.024
Subject(s) - inflammation , hippocampal formation , receptor , cerebrospinal fluid , neuroscience , disease , lipoxin , alzheimer's disease , medicine , biology , pathology
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 A 4 (LXA 4 ) were reduced in AD, both in the CSF and hippocampus. An enzyme involved in LXA 4 synthesis and two SPM receptors were elevated in AD brains. LXA 4 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.