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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2015

Open Access 01-12-2015 | Research article

Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits

Authors: Zhiqiang Xu, Na Xiao, Yali Chen, Huang Huang, Charles Marshall, Junying Gao, Zhiyou Cai, Ting Wu, Gang Hu, Ming Xiao

Published in: Molecular Neurodegeneration | Issue 1/2015

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Abstract

Background

Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.

Results

Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.

Conclusions

These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.
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Metadata
Title
Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits
Authors
Zhiqiang Xu
Na Xiao
Yali Chen
Huang Huang
Charles Marshall
Junying Gao
Zhiyou Cai
Ting Wu
Gang Hu
Ming Xiao
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2015
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-015-0056-1

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Depletion of highly abundant proteins from human cerebrospinal fluid: a cautionary note