CSF microRNA Profiling in Alzheimer's Disease: a Screening and Validation Study

CSF microRNA Profiling in Alzheimer's Disease: a Screening and Validation Study
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DOI:
10.1007/s12035-016-0106-x
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发表时间:
2017-11-01
影响因子:
5.1
通讯作者:
Antonell, Anna
Antonell, Anna
中科院分区:
医学2区
文献类型:
--
作者:
Dangla-Valls, Adria;Molinuevo, Jose Luis;Antonell, Anna

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microRNA(miRNAs)是一类短的非编码RNA分子,通过转录后抑制靶基因的表达来调控基因的表达。它们已被证明与阿尔茨海默病(AD)的病理生理学有关,并被提议作为疾病生物标志物。在目前的工作中,我们研究了754个miRNAs在AD患者和对照组脑脊液(CSF)中的表达水平。我们已经探索了第一筛选队列(N = 20),并选择了12种miRNA在第二独立验证队列(N = 69)中进行进一步测试。我们已经发现AD CSF中miR-222和miR-125 b的显著上调。其中,miR-222与AD的关联是新的,并且在此首次报道,而miR-125 b的上调先前已在AD脑中报道。然而,我们没有发现与先前与AD相关的其他miRNAs的关联。我们的研究结果揭示了AD潜在的病理生理过程,也指出了CSF miRNA检测和数据分析中共识程序的必要性。
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression through post-transcriptional repression of target genes. They have been shown to be implicated in the pathophysiology of Alzheimer's disease (AD) and proposed as disease biomarkers. In the present work, we have studied the expression levels of 754 miRNAs in cerebrospinal fluid (CSF) from AD patients and control subjects. We have explored a first screening cohort (N = 20) and selected 12 miRNAs to be further tested in a second independent validation cohort (N = 69). We have found a significant upregulation of miR-222 and miR-125b in AD CSF. Of these, the association of miR-222 with AD is novel and reported here for the first time whereas upregulation of miR-125b has been previously reported in AD brain. Yet we do not find association with other miRNAs which were previously linked to AD. Our results shed light on potential underlying pathophysiological processes of AD and also point out the need for consensus procedures in CSF miRNA detection and data analysis.