microRNA Profiles in Parkinson's Disease Prefrontal Cortex.

Objective: The goal of this study was to compare the microRNA (miRNA) profile of Parkinson's disease (PD) frontal cortex with normal control brain, allowing for the identification of PD specific signatures as well as study the disease-related phenotypes of onset age and dementia. Methods: Small RNA sequence analysis was performed from prefrontal cortex for 29 PD samples and 33 control samples. After sample QC, normalization and batch correction, linear regression was employed to identify miRNAs altered in PD, and a PD classifier was developed using weighted voting class prediction. The relationship of miRNA levels to onset age and PD with dementia (PDD) was also characterized in case-only analyses. Results: One twenty five miRNAs were differentially expressed in PD at a genome-wide level of significance (FDR q < 0.05). A set of 29 miRNAs classified PD from non-diseased brain (93.9% specificity, 96.6% sensitivity). The majority of differentially expressed miRNAs (105/125) showed an ordinal relationship from control, to PD without dementia (PDN), to PDD. Among PD brains, 36 miRNAs classified PDD from PDN (sensitivity = 81.2%, specificity = 88.9%). Among differentially expressed miRNAs, miR-10b-5p had a positive association with onset age (q = 4.7e-2). Conclusions: Based on cortical miRNA levels, PD brains were accurately classified from non-diseased brains. Additionally, the PDD miRNA profile exhibited a more severe pattern of alteration among those differentially expressed in PD. To evaluate the clinical utility of miRNAs as potential clinical biomarkers, further characterization and testing of brain-related miRNA alterations in peripheral biofluids is warranted.

目的：本研究旨在比较帕金森病（PD）额叶皮质与正常对照大脑的微小核糖核酸（miRNA）图谱，以识别PD特异性特征，并研究发病年龄和痴呆等与疾病相关的表型。 方法：对29例PD样本和33例对照样本的前额叶皮质进行小核糖核酸序列分析。在样本质量控制、标准化和批次校正后，采用线性回归来识别PD中改变的miRNAs，并使用加权投票分类预测开发了一种PD分类器。在仅病例分析中还描述了miRNA水平与发病年龄以及伴有痴呆的PD（PDD）之间的关系。 结果：在全基因组显著水平（错误发现率q < 0.05）上，有125种miRNAs在PD中差异表达。一组29种miRNAs可将PD与非患病大脑区分开来（特异性为93.9%，敏感性为96.6%）。大多数差异表达的miRNAs（125种中的105种）从对照组到无痴呆的PD（PDN）再到PDD呈现出一种顺序关系。在PD大脑中，36种miRNAs可将PDD与PDN区分开来（敏感性 = 81.2%，特异性 = 88.9%）。在差异表达的miRNAs中，miR - 10b - 5p与发病年龄呈正相关（q = 4.7×10⁻²）。 结论：基于皮质miRNA水平，可准确地将PD大脑与非患病大脑区分开来。此外，在PD中差异表达的miRNAs中，PDD的miRNA图谱表现出更严重的改变模式。为了评估miRNAs作为潜在临床生物标志物的临床实用性，有必要对外周生物流体中与大脑相关的miRNA改变进行进一步的表征和测试。