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Batch prepared protein standards for cerebrospinal fluid (CSF) biomarkers for neurodegeneration.

机译:批量制备用于神经退行性脑脊髓液(CSF)生物标志物的蛋白质标准品。

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摘要

Immuno-assays are increasingly used for quantification of protein biomarkers for neurodegeneration. It has been proposed to use such cerebrospinal fluid (CSF) protein biomarkers as diagnostic tests for Alzheimer's disease. In two recent world-wide validation studies we found the analytical accuracy to be poor (inter-laboratory coefficient of variation, CV>10%) for CSF tau protein, CSF phospho-tau protein, CSF amyloid beta protein and the CSF neurofilament light chain protein. Retrospectively we suspected that the lack of preparation of accurate and consistent protein standards may have been one reason for the poor inter-laboratory CV. Here we confirm this hypothesis prospectively under standardised and optimised conditions. The CVs for CSF tau, CSF phospho-tau and CSF amyloid beta of individually prepared standards are 8%, 12% and 12% compared to significantly lower CVs for batch prepared standards (5%, 8%, 7%, respectively, p<0.05). This issue will need to be solved in order to ensure that the attempts to include these CSF protein biomarkers either as a diagnostic tool or a secondary outcome measure for treatment trials will be successful.
机译:免疫测定法越来越多地用于定量神经退行性病变的蛋白质生物标记物。已经提出使用这种脑脊髓液(CSF)蛋白生物标记物作为阿尔茨海默氏病的诊断测试。在最近的两项全球验证研究中,我们发现CSF tau蛋白,CSF磷酸tau蛋白,CSF淀粉样β蛋白和CSF神经丝轻链的分析准确性很差(实验室间变异系数,CV> 10%)。蛋白。回顾性地,我们怀疑缺乏准确和一致的蛋白质标准品的制备可能是造成实验室间简历差的原因之一。在这里,我们在标准化和优化的条件下前瞻性地证实了这一假设。单独制备的标准品的CSF tau,CSF磷酸化tau和CSF淀粉样蛋白β的CV为8%,12%和12%,而批量制备的标准品的CV则明显较低(分别为5%,8%,7%,p < 0.05)。为了确保将这些CSF蛋白生物标志物作为治疗工具的诊断工具或次要结果指标纳入尝试,将需要成功解决该问题。

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