临床环境中 CSF 阿尔茨海默病生物标志物的站点间变异性。

Intersite variability of CSF Alzheimer's disease biomarkers in clinical setting.

机构信息

Centre Memoire Ressources Recherche Paris Nord Ile-de-France, AP-HP, Saint Louis - Lariboisiere - Fernand Widal Hospital, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.

出版信息

Alzheimers Dement. 2013 Jul;9(4):406-13. doi: 10.1016/j.jalz.2012.06.006. Epub 2012 Nov 8.

DOI:10.1016/j.jalz.2012.06.006

PMID:23141384

Abstract

BACKGROUND

The assessment of total tau, phosphorylated tau (pTau-181) and amyloid beta (Aβ 1-42) concentrations in the cerebrospinal fluid (CSF) of subjects has been validated for the diagnosis of Alzheimer's disease (AD). Although these measurements have shown some variability, little is known about their intersite variability in clinical settings.

METHODS

A total of 880 subjects (AD, n = 515; non-AD, n = 365) from three French memory centers were included. Receiver-operating characteristic analyses were performed to computerized area under curves (AUCs) and optimal thresholds for each biomarker in the three centers. A test-retest study was performed in a group of 32 CSF samples by repeated blind analysis of the three biomarkers using the same immunoassay batches in the three centers.

RESULTS

In the three centers, tau (AUC, 0.82-0.88) and pTau-181 (AUC, 0.83-0.89) outperformed Aβ 1-42 (AUC, 0.70 -0.73) to discriminate subjects with AD from those without AD. An intersite variation of mean levels and cutoffs was observed for the three biomarkers. This variation was higher for Aβ 1-42 (range of cutoff, 368-582 pg/mL) than for tau (range of cutoff, 289-353 pg/mL). In a test-retest study, the mean interlaboratory coefficients of variation were 12.2% for Aβ 1-42, 11.3% for tau, and 11.5% for pTau-181.

CONCLUSION

Intercenter variability of CSF biomarkers has been confirmed in a multisite cohort of subjects and can be improved in clinical settings. Efforts on harmonization of procedures should be encouraged to optimize the accuracy of CSF biomarkers in AD.

摘要

背景

对受试者脑脊液（CSF）中总 tau、磷酸化 tau（pTau-181）和淀粉样蛋白 β（Aβ 1-42）浓度的评估已被验证可用于诊断阿尔茨海默病（AD）。尽管这些测量方法已经显示出一定的变异性，但对于它们在临床环境中的站点间变异性知之甚少。

方法

共纳入来自法国三个记忆中心的 880 名受试者（AD，n=515；非 AD，n=365）。进行了受试者工作特征分析，以计算每个生物标志物在三个中心的计算机化曲线下面积（AUC）和最佳阈值。对 32 份 CSF 样本进行了测试-重测研究，通过在三个中心使用相同的免疫测定批次对三种生物标志物进行重复盲法分析。

结果

在三个中心，tau（AUC，0.82-0.88）和 pTau-181（AUC，0.83-0.89）优于 Aβ 1-42（AUC，0.70-0.73），可区分 AD 受试者和非 AD 受试者。三种生物标志物的平均水平和临界值存在站点间差异。这种变化对于 Aβ 1-42（临界值范围，368-582 pg/mL）高于 tau（临界值范围，289-353 pg/mL）。在测试-重测研究中，三种生物标志物的实验室间平均变异系数分别为 12.2%、11.3%和 11.5%。