title: Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits.
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 nonsignificant 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.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xiao
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Rehabilitation Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors.forename: Zhiyou
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China. mingx@njmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology*; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D019208:Brain-Derived Neurotrophic Factor