Aquaporin-4 polymorphisms predict amyloid burden and clinical outcome in the Alzheimer's disease spectrum
Aquaporin-4 polymorphisms predict amyloid burden and clinical outcome in the Alzheimer's disease spectrum
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DOI：
10.1016/j.neurobiolaging.2020.06.007
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发表时间：
2021-01-01
影响因子：
4.2
通讯作者：
Politis, Marios
中科院分区：
文献类型：
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作者：
Chandra, Avinash;Farrell, Chloe;Politis, Marios
假设淀粉样蛋白-β（A β）从脑中的清除由胶质淋巴系统通过水通道蛋白-4（AQP 4）水通道介导。AQP 4的遗传变异可能影响水通道功能、A β清除和临床结局。我们在100例A β阳性晚期轻度认知功能障碍（LMCI）或阿尔茨海默病（AD）患者中检测了AQP 4基因的单核苷酸多态性（SNP）是否与[F-18]Florbetapir PET上的A β神经病理学相关，并预测前驱AD患者的临床结局。AQP 4 SNP rs72878794与A β摄取减少相关，而rs 151244与A β摄取增加相关，增加了从MCI和LMCI转化为AD的风险，并增加了LMCI的4年认知能力下降率。AQP 4基因变异与A β积累、疾病阶段进展和认知能力下降相关。这种变化可能对应于胶质淋巴系统功能和大脑A β清除率的变化，并且可能是预测痴呆症谱系疾病负担的有用生物标志物。(C)2020爱思唯尔公司All rights reserved.
Clearance of amyloid-beta (A beta) from the brain is hypothesized to be mediated by the glymphatic system through aquaporin-4 (AQP4) water channels. Genetic variation of AQP4 may impact water channel function, A beta clearance, and clinical outcomes. We examined whether single-nucleotide polymorphisms (SNPs) of the AQP4 gene were related to A beta neuropathology on [F-18]Florbetapir PET in 100 A beta positive late mild cognitive impairment (LMCI) or Alzheimer's disease (AD) patients and were predictive of clinical outcome in prodromal AD patients. AQP4 SNP rs72878794 was associated with decreased A beta uptake, whereas rs151244 was associated with increased A beta uptake, increased risk of conversion from MCI and LMCI to AD, and an increased 4-year rate of cognitive decline in LMCI. AQP4 genetic variation was associated with A beta accumulation, disease stage progression, and cognitive decline. This variation may correspond to changes in glymphatic system functioning and brain A beta clearance and could be a useful biomarker in predicting disease burden for those on the dementia spectrum. (C) 2020 Elsevier Inc. All rights reserved.