Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes.
Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes.
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DOI：
10.3233/jad-160848
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Arai H
中科院分区：
文献类型：
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作者：
Jurjević I;Miyajima M;Ogino I;Akiba C;Nakajima M;Kondo A;Kikkawa M;Kanai M;Hattori N;Arai H
背景：出现典型的特发性常压性脑积水(INPH)三联症的患者通常会表现出额外的帕金森氏谱征。准确的鉴别诊断对脑脊液分流术的远期疗效有很大影响。目的：本研究的目的是寻找潜在的脑脊液微RNA(MiRNA)生物标志物，用于帕金森综合征的NPH模拟，以可靠地将其与INPH患者区分开来。方法：对2011年1月至2014年5月在两个中心接受治疗的81名可能患有 = 的患者(队列1，n = 55例；队列2，n ph 26例)进行研究。在这两个队列中，脑脊液样本分别来自临床诊断为INPH的患者(n = 21和n = 10)、可能的INPH伴帕金森病谱(PS)的患者(n = 18，n = 10)、可能的INPH合并阿尔茨海默病(AD)(n = 16)和未受影响的老年人(NC)(n = 6)。对脑脊液样本进行了三步qRT-PCR分析，以检测在两组中差异表达的miRNAs。结果：两组PS患者脑脊液中hSA-miR-4274的表达均降低(队列1：P <； 0.0001，队列2：P <； 0.0001)，并能较准确地区分PS与INPH(曲线下面积 = 0.908)。脑脊液中hSA-miR-4274的浓度与123I-多巴胺转运体扫描的特异性结合率呈正相关(r = -0.494，p = 0.044)。而脑脊液分流后PS组hsa-miR-4274水平显著升高。结论：脑脊液hsa-miR-4274水平可作为鉴别PS与INPH、AD和NC的指标。这可能对临床诊断和预测分流治疗反应是有用的。
Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer’s disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = –0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion. Conclusion: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.