From the Bioinformatics Program (E.R.R., R.H.M.), Boston University; Department of Neurology (J.C.L., J.B., R.H.M.), Boston University School of Medicine, MA; and Departments of Neurology and Psychiatry (J.H.B., J.S.P.) and Internal Medicine (J.S.), Carver College of Medicine, University of Iowa, Iowa City.
Neurology. 2018 Jan 23;90(4):e264-e272. doi: 10.1212/WNL.0000000000004844. Epub 2017 Dec 27.
To investigate the feasibility of microRNA (miRNA) levels in CSF as biomarkers for prodromal Huntington disease (HD).
miRNA levels were measured in CSF from 60 PREDICT-HD study participants using the HTG protocol. Using a CAG-Age Product score, 30 prodromal HD participants were selected based on estimated probability of imminent clinical diagnosis of HD (i.e., low, medium, high; n = 10/group). For comparison, participants already diagnosed (n = 15) and healthy controls (n = 15) were also selected.
A total of 2,081 miRNAs were detected and 6 were significantly increased in the prodromal HD gene expansion carriers vs controls at false discovery rate q < 0.05 (miR-520f-3p, miR-135b-3p, miR-4317, miR-3928-5p, miR-8082, miR-140-5p). Evaluating the miRNA levels in each of the HD risk categories, all 6 revealed a pattern of increasing abundance from control to low risk, and from low risk to medium risk, which then leveled off from the medium to high risk and HD diagnosed groups.
This study reports miRNAs as CSF biomarkers of prodromal and diagnosed HD. Importantly, miRNAs were detected in the prodromal HD groups furthest from diagnosis where treatments are likely to be most consequential and meaningful. The identification of potential biomarkers in the disease prodrome may prove useful in evaluating treatments that may postpone disease onset.
NCT00051324.
研究脑脊液（CSF）中 microRNA（miRNA）水平作为亨廷顿病（HD）前驱期生物标志物的可行性。
采用 HTG 方案，使用 PREDICT-HD 研究参与者的 CSF 测量 miRNA 水平。使用 CAG-年龄产物评分，根据 HD 临床诊断的预期可能性（即低、中、高；n=10/组），选择 30 名前驱期 HD 参与者。为了比较，还选择了已经诊断的参与者（n=15）和健康对照者（n=15）。
共检测到 2081 种 miRNA，6 种 miRNA 在前驱期 HD 基因扩增携带者与对照组相比在假发现率 q<0.05 时显著增加（miR-520f-3p、miR-135b-3p、miR-4317、miR-3928-5p、miR-8082、miR-140-5p）。评估每个 HD 风险类别中的 miRNA 水平，所有 6 种 miRNA 都显示出从对照组到低风险、从低风险到中风险的丰度增加的模式，然后从中风险到高风险和诊断为 HD 的组中水平稳定。
本研究报告了作为前驱期和诊断性 HD 的 CSF 生物标志物的 miRNA。重要的是，在距离诊断最远的前驱期 HD 组中检测到了 miRNA，这可能是治疗最具影响和意义的阶段。在疾病前驱期识别潜在的生物标志物可能有助于评估可能推迟疾病发作的治疗方法。
NCT00051324。
