Resolution of inflammation is altered in Alzheimer's disease
- 31 December 2014
- journal article
- research article
- Published by Wiley in Alzheimer's & Dementia
- Vol. 11 (1), 40-50
- https://doi.org/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 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. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.Funding Information
- Vetenskapsrådet (072194)
- Swedish Brain Power
- Knut och Alice Wallenbergs Stiftelse
- Karolinska Institutet
- Stiftelsen för Gamla Tjänarinnor
- Gun och Bertil Stohnes Stiftelse
- Petrus och Augusta Hedlunds Stiftelse
- National Institutes of Health (P01GM095467, GM038765)
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