Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
Alzheimers Dement. 2013 May;9(3):251-61. doi: 10.1016/j.jalz.2013.01.010.
The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories.
Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection.
A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1-42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP).
The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
脑脊液（CSF）生物标志物β淀粉样蛋白 1-42、总 tau 和磷酸化 tau 越来越多地用于阿尔茨海默病（AD）的研究和患者管理。然而，在实验室之间和实验室内部，生物标志物的测量存在很大差异。
使用阿尔茨海默病协会质量控制计划的前九轮的数据来定义分析变异性的程度和来源。在每一轮中，临床神经化学实验室（瑞典莫伦达尔）制备的三份 CSF 样本通过单分析物酶联免疫吸附测定（ELISA）、多重 xMAP 测定或电化学发光检测的免疫测定进行分析。
共有 84 个实验室参与。实验室之间的变异系数（CV）约为 20%至 30%；批内 CV 小于 5%至 10%；实验室内部的纵向 CV 为 5%至 19%。有趣的是，个体实验室中纵向实验室内部 CV 因生物标志物而异，这表明其中一部分是依赖于检测的。试剂盒批次之间和实验室之间的变异性都对β淀粉样蛋白 1-42 的测量有重大影响，但对于总 tau 和磷酸化 tau，试剂盒批次之间的影响比实验室之间的影响小得多。尽管存在测量变异性，但样本分类的实验室间一致性仍然很高（使用预先设定的 AD 切点，ELISA 为 15 个样本中的 18 个，xMAP 为 12 个样本中的 18 个）。
总体变异性仍然过高，无法为特定预期用途分配通用的生物标志物截止值。每个实验室都必须确保其测量的纵向稳定性，并使用内部合格的截止值。进一步标准化实验室程序和提高试剂盒性能可能会增加 CSF AD 生物标志物对研究人员和临床医生的有用性。
