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微小RNA作为阿尔茨海默病潜在的血液表观遗传生物标志物。

Micro RNA as a potential blood-based epigenetic biomarker for Alzheimer's disease.

作者信息

Fransquet Peter D, Ryan Joanne

机构信息

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Victoria, Australia; Disease Epigenetics, Murdoch Childrens Research Institute, and The University of Melbourne, Parkville, 3052, Victoria, Australia.

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, Victoria, Australia; Disease Epigenetics, Murdoch Childrens Research Institute, and The University of Melbourne, Parkville, 3052, Victoria, Australia; INSERM, U1061, Neuropsychiatrie, Recherche Clinique et Epidémiologique, Univ. Montpellier, Montpellier 34000, France.

出版信息

Clin Biochem. 2018 Aug;58:5-14. doi: 10.1016/j.clinbiochem.2018.05.020. Epub 2018 Jun 6.

Abstract

As the prevalence of Alzheimer's disease (AD) increases, the search for a definitive, easy to access diagnostic biomarker has become increasingly important. Micro RNA (miRNA), involved in the epigenetic regulation of protein synthesis, is a biological mark which varies in association with a number of disease states, possibly including AD. Here we comprehensively review methods and findings from 26 studies comparing the measurement of miRNA in blood between AD cases and controls. Thirteen of these studies used receiver operator characteristic (ROC) analysis to determine the diagnostic accuracy of identified miRNA to predict AD, and three studies did this with a machine learning approach. Of 8098 individually measured miRNAs, 23 that were differentially expressed between AD cases and controls were found to be significant in two or more studies. Only six of these were consistent in their direction of expression between studies (miR-107, miR-125b, miR-146a, miR-181c, miR-29b, and miR-342), and they were all shown to be down regulated in individuals with AD compared to controls. Of these directionally concordant miRNAs, the strongest evidence was for miR-107 which has also been shown in previous studies to be involved in the dysregulation of proteins involved in aspects of AD pathology, as well as being consistently downregulated in studies of AD brains. We conclude that imperative to the discovery of reliable and replicable miRNA biomarkers of AD, standardised methods of measurements, appropriate statistical analysis, utilization of large datasets with machine learning approaches, and comprehensive reporting of findings is urgently needed.

摘要

随着阿尔茨海默病(AD)患病率的上升,寻找一种确定的、易于获取的诊断生物标志物变得越来越重要。微小RNA(miRNA)参与蛋白质合成的表观遗传调控,是一种与多种疾病状态相关的生物标志物,可能包括AD。在此,我们全面回顾了26项比较AD病例和对照血液中miRNA测量的研究方法和结果。其中13项研究使用受试者工作特征(ROC)分析来确定所鉴定的miRNA预测AD的诊断准确性,3项研究采用机器学习方法进行此项分析。在8098个单独测量的miRNA中,发现AD病例和对照之间差异表达的23个miRNA在两项或更多研究中具有显著性。其中只有6个在各研究中的表达方向一致(miR-107、miR-125b、miR-146a、miR-181c、miR-29b和miR-342),并且与对照相比,它们在AD个体中均显示下调。在这些方向一致的miRNA中,最有力的证据是miR-107,在先前的研究中也已表明它参与AD病理方面相关蛋白质的失调,并且在AD脑研究中一直下调。我们得出结论,迫切需要标准化的测量方法、适当的统计分析、利用机器学习方法处理大型数据集以及全面报告研究结果,以便发现可靠且可重复的AD miRNA生物标志物。

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