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.
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This work was supported by grants from the National Natural Science Foundation of China (No 81271210) and the Natural Science Foundation of Jiangsu Educational Department (14KJA320001).
Xu, Zhiqiang; Xiao, Na; Chen, Yali; Huang, Huang; Marshall, Charles; Gao, Junying; Cai, Zhiyou; Wu, Ting; Hu, Gang; and Xiao, Ming, "Deletion of Aquaporin-4 in APP/PS1 Mice Exacerbates Brain Aβ Accumulation and Memory Deficits" (2015). Center for Excellence in Rural Health Faculty Publications. 6.