Kruse Niels, Heslegrave Amanda, Gupta Vandana, Foiani Martha, Villar-Piqué Anna, Schmitz Matthias, Lehmann Sylvain, Teunissen Charlotte, Blennow Kaj, Zetterberg Henrik, Mollenhauer Brit, Zerr Inga, Llorens Franc
Institute for Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
Alzheimers Dement (Amst). 2018 Jul 7;10:461-470. doi: 10.1016/j.dadm.2018.06.005. eCollection 2018.
Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay.
Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non-Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories.
A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%-11.39%. Overall, 97% of samples were correctly diagnosed.
The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.
散发性克雅氏病患者脑脊液中α-突触核蛋白水平升高。然而，这种生物标志物的临床价值仍有待确定。在本研究中，我们通过使用电化学发光分析法探讨了临床验证参数和实验室间的可重复性。
对总共188例散发性克雅氏病和非克雅氏病病例的脑脊液α-突触核蛋白进行定量，以确定敏感性和特异性值以及批次间的变异性。在六个独立实验室对另外70例病例进行了两轮比对试验。
在鉴别散发性克雅氏病方面，敏感性达到93%，特异性达到96%。批次间未检测到差异。实验室间变异系数的平均值为23%，实验室内部变异系数范围为2.70%-11.39%。总体而言，97%的样本得到了正确诊断。
本文验证的α-突触核蛋白检测方法在识别克雅氏病病例方面稳健、准确且可重复。因此，它已准备好在临床实践中应用，以辅助克雅氏病的诊断。
