脑脊液 AD 研究中一个重要潜在混杂因素的鉴定：分液器体积。

Identification of an important potential confound in CSF AD studies: aliquot volume.

出版信息

Clin Chem Lab Med. 2013 Dec;51(12):2311-7. doi: 10.1515/cclm-2013-0293.

DOI:10.1515/cclm-2013-0293

Abstract

BACKGROUND

Cerebrospinal fluid (CSF) amyloid β1-42 (Aβ1-42), total tau (T-tau) and phosphorylated tau181 (P-tau) are finding increasing utility as biomarkers of Alzheimer's disease (AD). The purpose of this study was to determine whether measured CSF biomarker concentrations were affected by aliquot storage volume and whether addition of detergent-containing buffer mitigates any observed effects.

METHODS

AD and control CSF was distributed into polypropylene tubes in aliquots of different volumes (50-1500 μL). Aβ1-42, T-tau and P-tau were measured with and without addition of Tween 20 (0.05%).

RESULTS

Measured concentrations of Aβ1-42 increased two-fold with aliquot storage volume. A volume increase of 10 µL caused an Aβ1-42 increase of 0.95 pg/mL [95% confidence interval (CI) 0.36-1.50, p=0.02] in controls, and 0.60 pg/mL (CI 0.23-0.98 pg/mL, p=0.003) in AD samples. Following addition of Tween 20, the positive relationship between Aβ1-42 and aliquot volume disappeared. T-tau and P-tau were not significantly affected.

CONCLUSIONS

CSF aliquot storage volume has a significant impact on the measured concentration of Aβ1-42. The introduction of a buffer detergent at the initial aliquoting stage may be an effective solution to this problem.

摘要

背景

脑脊液（CSF）中的β淀粉样蛋白 1-42（Aβ1-42）、总 tau（T-tau）和磷酸化 tau181（P-tau）作为阿尔茨海默病（AD）的生物标志物，其应用越来越广泛。本研究旨在确定 CSF 生物标志物的测量浓度是否受等分存储体积的影响，以及添加含洗涤剂的缓冲液是否可以减轻任何观察到的影响。

方法

将 AD 和对照 CSF 分配到不同体积（50-1500μL）的聚丙烯管中。在添加或不添加吐温 20（0.05%）的情况下测量 Aβ1-42、T-tau 和 P-tau。

结果

等分存储体积增加时，Aβ1-42 的测量浓度增加了一倍。等分体积增加 10μL 会使对照组的 Aβ1-42 增加 0.95pg/mL（95%置信区间[CI]0.36-1.50，p=0.02），AD 样本中增加 0.60pg/mL（CI0.23-0.98pg/mL，p=0.003）。添加吐温 20 后，Aβ1-42 与等分体积之间的正相关关系消失。T-tau 和 P-tau 不受显著影响。