Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits
Z Xu, N Xiao, Y Chen, H Huang, C Marshall… - Molecular …, 2015 - Springer
Z Xu, N Xiao, Y Chen, H Huang, C Marshall, J Gao, Z Cai, T Wu, G Hu, M Xiao
Molecular neurodegeneration, 2015•SpringerBackground 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 …
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 …
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.
Springer
