Dataset Information

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC4275415 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Publications

Resolution of inflammation is altered in Alzheimer's disease.

Wang Xiuzhe X Zhu Mingqin M Hjorth Erik E Cortés-Toro Veronica V Eyjolfsdottir Helga H Graff Caroline C Nennesmo Inger I Palmblad Jan J Eriksdotter Maria M Sambamurti Kumar K Fitzgerald Jonathan M JM Serhan Charles N CN Granholm Ann-Charlotte AC Schultzberg Marianne M

Alzheimer's & dementia : the journal of the Alzheimer's Association 20140212 1

<h4>Background</h4>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).<h4>Methods</h4>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 ...[more]

PMID: 24530025

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Project description:Alzheimer's disease is the commonest form of dementia, but its cause still remains elusive. It is characterized by neurodegeneration, with amyloid-beta and tau aggregation. Recently, however, the roles of the vasculature and the neurovascular unit are being highlighted as important for disease progression. In particular, there is reduced microvascular density, and altered gene expression in vascular and glial cells. Structural changes naturally impact the functioning of the neurovascular unit, and the goal of the study was to quantify the corresponding changes in vivo, non-invasively. Our assessment is based on recordings of brain oxygenation, neuronal and cardiorespiratory activities, captured by functional near-infrared spectroscopy, electroencephalogram, electrocardiogram and respiration effort, respectively. Two groups were compared: an Alzheimer's disease group (N = 19) and a control group (N = 20) of similar age. The time-series were analysed using methods that can capture multi-scale and time-varying oscillations such as the wavelet transform power and wavelet phase coherence. The Alzheimer's disease group shows a significant decrease in the power of brain oxygenation oscillations compared to the control group. There is also a significant global reduction in the phase coherence between brain oxygenation time-series. The neurovascular phase coherence around 0.1 Hz is also significantly reduced in the Alzheimer's disease group. In addition, the average respiration rate is increased in the Alzheimer's disease group compared to the control group. We show that the phase coherence between vascular and neuronal activities is reduced in Alzheimer's disease compared to the control group, indicating altered functioning of the neurovascular unit. The brain oxygenation dynamics reveals reduced power and coordination of oscillations, especially in frequency ranges that are associated with vasomotion. This could lead to reduced oxygen delivery to the brain, which could affect ATP production, and potentially reduce amyloid-beta clearance. These changes in neurovascular dynamics have potential for early diagnosis, as a marker of disease progression, and for evaluating the effect of interventions.

Dataset Information

Resolution of inflammation is altered in Alzheimer's disease.

Background

Methods

Results

Conclusions

Publications

Resolution of inflammation is altered in Alzheimer's disease.

Similar Datasets

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