已知脑水通道蛋白(AQP)通道1、4和9的表达改变与神经病理学AD进展相关。但其他AQP类别在神经系统疾病中的可能作用仍未得到充分研究.通过对AllenBrainAtlas数据库中微阵列RNAseq表达数据的统计分析,比较了健康和阿尔茨海默病(AD)大脑中所有13种人类AQP亚型的转录水平。以前没有报道,AQP0、6和10以转录物水平存在于人脑中。三个受AD影响的大脑区域,海马(HIP),顶叶皮质(PCx)和颞叶皮质(TCx),在三个亚组中进行了评估:年轻对照组(n=6,年龄24-57岁);老年对照组(n=26,年龄78-99岁);和AD队列(n=12,年龄79-99岁)。观察到AQP转录物水平作为受试者年龄(以年为单位)的函数的显著正相关(p<10-10)。与大脑区域相关的差异表达,年龄,和AD诊断,特别是在HIP和皮质区域之间。有趣的是,与年轻对照相比,AD中上调的三类AQP(0、6和8)对H2O2具有渗透性。其中,在HIP中,AQP0和8在TCx和AQP6中增加,提示AQPs在AD相关氧化应激中的作用。这里的结果是第一个证明AQP通道在人脑中的表达谱比以前认为的更加多样化,和转录水平受年龄和AD状态的影响。活性氧应激与神经退行性疾病风险之间的关联突出了AQP0、6、8和10作为潜在的治疗靶标。
The altered expression of known brain Aquaporin (AQP) channels 1, 4 and 9 has been correlated with neuropathological AD progression, but possible roles of other AQP classes in neurological disease remain understudied. The levels of transcripts of all thirteen human AQP subtypes were compared in healthy and Alzheimer\'s disease (AD) brains by statistical analyses of microarray RNAseq expression data from the Allen Brain Atlas database. Previously unreported, AQPs 0, 6 and 10, are present in human brains at the transcript level. Three AD-affected brain regions, hippocampus (HIP), parietal cortex (PCx) and temporal cortex (TCx), were assessed in three subgroups: young controls (n = 6, aged 24-57); aged controls (n = 26, aged 78-99); and an AD cohort (n = 12, aged 79-99). A significant positive correlation (p < 10-10) was seen for AQP transcript levels as a function of the subject\'s age in years. Differential expressions correlated with brain region, age, and AD diagnosis, particularly between the HIP and cortical regions. Interestingly, three classes of AQPs (0, 6 and 8) upregulated in AD compared to young controls are permeable to H2O2. Of these, AQPs 0 and 8 were increased in TCx and AQP6 in HIP, suggesting a role of AQPs in AD-related oxidative stress. The outcomes here are the first to demonstrate that the expression profile of AQP channels in the human brain is more diverse than previously thought, and transcript levels are influenced by both age and AD status. Associations between reactive oxygen stress and neurodegenerative disease risk highlight AQPs 0, 6, 8 and 10 as potential therapeutic targets.