Comparative study of cerebrospinal fluid α-synuclein seeding aggregation assays for diagnosis of Parkinson's disease
Comparative study of cerebrospinal fluid α-synuclein seeding aggregation assays for diagnosis of Parkinson's disease
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DOI：
10.1002/mds.27646
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发表时间：
2019-04-01
影响因子：
8.6
通讯作者：
Soto, Claudio
中科院分区：
文献类型：
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作者：
Kang, Un Jung;Boehme, Amelia K.;Soto, Claudio
背景帕金森病的诊断主要基于临床标准，可能不准确。反映正在进行的致病过程的生物标记物，如α-突触核蛋白聚集，可能会提高诊断的准确性，并允许监测疾病进展。虽然α-突触核蛋白聚集分析已经发表，但重复性、标准化和验证是将其发展为临床生物标记物的关键挑战。目的使用来自相同PD患者和来自BioFIND队列的健康对照的样本，交叉验证两种用于检测脑脊液中致病低聚α-突触核蛋白种类的α-突触核蛋白种子聚集试验。方法脑脊液标本由两个独立的实验室进行盲法检测。BioFIND以临床典型的中度PD患者和非疾病对照的标准化生物样本收集为特色。用蛋白质误折叠循环扩增(Soto Lab)和实时抖动诱导转换(Green Lab)检测α-突触核蛋白聚集。结果由一位独立的统计师分析。结果105例帕金森病患者和79例健康对照脑脊液标本检测结果的符合率为92%。受试者工作特征曲线分析用于诊断帕金森病与健康对照的曲线下面积分别为0.93(蛋白质错误折叠循环扩增)、0.89(实时抖动诱导转换)和0.95(仅考虑一致性检测结果)。假阳性和阴性患者的临床特征与真阴性和阳性患者无明显差异。结论α-突触核蛋白种子凝集试验用于帕金森病的诊断是可靠的、重复性好的。检测参数与包括疾病严重程度或病程在内的临床参数没有相关性。这项检测对帕金森病的诊断具有很高的准确性，可能会影响临床实践和临床试验。(C)2019年提交人。《运动障碍》由威利期刊公司代表国际帕金森和运动障碍协会出版。
Background PD diagnosis is based primarily on clinical criteria and can be inaccurate. Biological markers, such as alpha-synuclein aggregation, that reflect ongoing pathogenic processes may increase diagnosis accuracy and allow disease progression monitoring. Though alpha-synuclein aggregation assays have been published, reproducibility, standardization, and validation are key challenges for their development as clinical biomarkers. Objective To cross-validate two alpha-synuclein seeding aggregation assays developed to detect pathogenic oligomeric alpha-synuclein species in CSF using samples from the same PD patients and healthy controls from the BioFIND cohort. Methods CSF samples were tested by two independent laboratories in a blinded fashion. BioFIND features standardized biospecimen collection of clinically typical moderate PD patients and nondisease controls. alpha-synuclein aggregation was measured by protein misfolding cyclic amplification (Soto lab) and real-time quaking-induced conversion (Green lab). Results were analyzed by an independent statistician. Results Measuring 105 PD and 79 healthy control CSF samples, these assays showed 92% concordance. The areas under the curve from receiver operating characteristic curve analysis for the diagnosis of PD versus healthy controls were 0.93 for protein misfolding cyclic amplification, 0.89 for real-time quaking-induced conversion, and 0.95 when considering only concordant assay results. Clinical characteristics of false-positive and -negative subjects were not different from true-negative and -positive subjects, respectively. Conclusions These alpha-synuclein seeding aggregation assays are reliable and reproducible for PD diagnosis. Assay parameters did not correlate with clinical parameters, including disease severity or duration. This assay is highly accurate for PD diagnosis and may impact clinical practice and clinical trials. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.