Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.

Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.
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DOI:
10.1111/jnc.14569
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发表时间:
2019-04
影响因子:
4.7
通讯作者:
Zetterberg H
Zetterberg H
中科院分区:
医学2区
文献类型:
--
作者:
Mollenhauer B;Bowman FD;Drake D;Duong J;Blennow K;El-Agnaf O;Shaw LM;Masucci J;Taylor P;Umek RM;Dunty JM;Smith CL;Stoops E;Vanderstichele H;Schmid AW;Moniatte M;Zhang J;Kruse N;Lashuel HA;Teunissen C;Schubert T;Dave KD;Hutten SJ;Zetterberg H

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α‐突触核蛋白是路易小体的主要成分,也是路易小体常见的神经退行性疾病的候选生物标志物,包括帕金森病和路易小体痴呆。大量文献表明,这些疾病的特征是脑脊液(CSF)中α‐突触核蛋白浓度降低,与健康对照相比,浓度重叠,且研究之间存在差异。有几个原因可以解释这种差异,包括技术原因,如测定间和实验室间的差异(可重复性)。我们比较了四种免疫化学方法用于定量50个独特脑脊液样品中的α‐突触核蛋白浓度。所有方法都被设计用于捕获脑脊液中大多数现有的α - synuclein形式(“总”α - synuclein)。虽然4种方法的回归线斜率不同,但均具有较高的分析精密度,实验室间相关性较好(R 2 0.83 ~ 0.99),实验室间相关性较好(R 2 0.64 ~ 0.93)。使用共同的参考CSF样品减少了检测方法和技术之间α‐突触核蛋白浓度的差异。还介绍了免疫沉淀质谱(IP‐MS)方法的试验数据。我们的结果表明,四种免疫化学方法和IP - MS方法测量相似形式的α -突触核蛋白,并且一个共同的参考物质可以使免疫测定结果协调一致。
α‐Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α‐synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter‐assay and inter‐laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α‐synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α‐synuclein forms in CSF (‘total’ α‐synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R 2 0.83–0.99), and good correlation with each other (R 2 0.64–0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α‐synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP‐MS) method is also presented. Our results suggest that the four immunochemical methods and the IP‐MS method measure similar forms of α‐synuclein and that a common reference material would allow harmonization of results between immunoassays.
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