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

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

Research output: Contribution to journalArticlepeer-review

316 Scopus citations

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.

Original languageEnglish
Article number56
JournalMolecular Neurodegeneration
Volume10
Issue number1
DOIs
StatePublished - Nov 2 2015

Bibliographical note

Publisher Copyright:
© 2015 Xu et al.

Keywords

  • AQP4
  • Alzheimer's disease
  • Amyloid-beta
  • Astrocytes
  • Paravascular pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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