A blood based 12-miRNA signature of Alzheimer disease patients.
A blood based 12-miRNA signature of Alzheimer disease patients.
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DOI：
10.1186/gb-2013-14-7-r78
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发表时间：
2013-07-29
期刊：
影响因子：
12.3
通讯作者：
Keller A
中科院分区：
文献类型：
--
作者：
Leidinger P;Backes C;Deutscher S;Schmitt K;Mueller SC;Frese K;Haas J;Ruprecht K;Paul F;Stähler C;Lang CJ;Meder B;Bartfai T;Meese E;Keller A
阿尔茨海默病（AD）是最常见的痴呆形式，但鉴定可靠的、早期的和非侵入性的生物标志物仍然是一个重大挑战。我们提出了一种新的基于miRNA的签名，用于从血液样品中检测AD。我们对来自48名AD患者和22名未受影响的对照的血液样本的miRNA进行了下一代测序，总共产生了140种表达水平显著变化的独特成熟miRNA。其中，82个在AD患者样品中具有较高丰度，58个具有较低丰度。我们选择了一组12种miRNAs对202个样本进行RT-qPCR分析，这些样本不仅包括AD患者和健康对照，还包括患有其他CNS疾病的患者。这些包括轻度认知障碍，这被认为是AD发展之前的过渡期，以及多发性硬化症，帕金森病，重度抑郁症，双相情感障碍和精神分裂症。选择的12种miRNA的miRNA靶富集分析表明miRNA参与神经系统发育、神经元投射、神经元投射发育和神经元投射形态发生。使用这个12-miRNA标签，我们区分AD和对照的准确性为93%，特异性为95%，灵敏度为92%。AD与其他神经系统疾病的鉴别准确率在74%至78%之间。其他CNS疾病与对照的区分产生甚至更高的准确性。这些数据表明，血液中失调的miRNA可能用作诊断AD或其他神经系统疾病的生物标志物。
Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.
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影响因子：
4.5
作者：
Guo, Sheng-Zhen;Huang, Ke;He, Lin
通讯作者：
He, Lin
DOI：
10.3233/jad-2012-129016
发表时间：
2013
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Braskie MN;Toga AW;Thompson PM
通讯作者：
Thompson PM
影响因子：
64.8
作者：
Gandy, Sam
通讯作者：
Gandy, Sam
影响因子：
3.7
作者：
Bauer AS;Keller A;Costello E;Greenhalf W;Bier M;Borries A;Beier M;Neoptolemos J;Büchler M;Werner J;Giese N;Hoheisel JD
通讯作者：
Hoheisel JD
影响因子：
14
作者：
Brookmeyer, Ron;Johnson, Elizabeth;Arrighi, H. Michael
通讯作者：
Arrighi, H. Michael