Resolution of inflammation is altered in Alzheimer's disease

阿尔茨海默病的炎症消退方式发生改变

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作者:Xiuzhe Wang, Mingqin Zhu, Erik Hjorth, Veronica Cortés-Toro, Helga Eyjolfsdottir, Caroline Graff, Inger Nennesmo, Jan Palmblad, Maria Eriksdotter, Kumar Sambamurti, Jonathan M Fitzgerald, Charles N Serhan, Ann-Charlotte Granholm, Marianne Schultzberg

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).

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.

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.

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