Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls.
Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls.
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DOI：
10.1371/journal.pone.0197329
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
FTLDc study group
中科院分区：
文献类型：
--
作者：
Denk J;Oberhauser F;Kornhuber J;Wiltfang J;Fassbender K;Schroeter ML;Volk AE;Diehl-Schmid J;Prudlo J;Danek A;Landwehrmeyer B;Lauer M;Otto M;Jahn H;FTLDc study group
关于额颞叶变性中循环miRNA的信息非常有限，并且迄今为止相互矛盾的结果使阿尔茨海默病的解释变得复杂。在本研究中，我们I）从德国的多个临床中心收集样本，II）定义了3个具有高样本量的同质患者组（bvFTD n = 48，AD n = 48，认知健康对照n = 44），III）比较CSF和血清样品中的表达水平，以及IV）通过使用基于SYBR的MIQE兼容方案检测有限的一组miRNA。绿色miRCURY检测已被证明可靠，可产生可重现的结果。我们纳入了几项质量控制措施，以识别和减少技术差异，从而提高数据的可靠性。我们发现在CSF中测量的循环miRNA的表达水平与血清中的水平不相关。使用聚类分析，我们发现血清中的表达模式部分反映了基因组组织和与特定miRNA家族的联系，并且在bvFTD、AD和对照组中发生了特异性改变。应用因子分析，我们确定了一个以miRNA特征为特征的3因子模型，该模型解释了80%的方差，健康对照组的准确率为97%，bvFTD为77%，AD为72%。MANOVA证实了BH校正显著性下的miR-320 a和miR-26 b-5 p等信号，与健康对照相比，这些信号对区分bvFTD病例和AD病例的贡献最大，分别为96%的灵敏度和90%的特异性，以及89%的灵敏度和特异性。相关性分析显示，来自3-因子模型的miRNA也与蛋白质生物标志物淀粉样蛋白-β 1 -42和磷酸化神经丝重链的水平相关，表明它们在监测进行性神经元变性中的潜在作用。我们的数据表明，无需预扩增即可重复测定血清和CSF中的miRNA，并且血清中包含更高的表达信号，表明与CSF中检测到的信号相比，对bvFTD、AD和健康对照进行分类的能力总体更好。
Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer’s disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF.
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DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
64.8
作者：
Baker, Matt;Mackenzie, Ian R.;Hutton, Mike
通讯作者：
Hutton, Mike
影响因子：
6.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
血清中 microRNA 的表征：一类用于诊断癌症和其他疾病的新型生物标志物
影响因子：
44.1
作者：
Chen, Xi;Ba, Yi;Zhang, Chen-Yu
通讯作者：
Zhang, Chen-Yu