Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Alzheimers Dis. 2012;31(2):439-45. doi: 10.3233/JAD-2012-120082.
The best-studied biomarkers of Alzheimer's disease (AD) are the pathologically-linked cerebrospinal fluid (CSF) proteins amyloid-β 42 (Aβ(1-42)), total tau (t-tau), and tau phosphorylated on amino acid 181 (p-tau(181)). Many laboratories measure these proteins using enzyme-linked immunosorbent assay (ELISA). Multiplex xMAP Luminex is a semi-automated assay platform with reduced intra-sample variance, which could facilitate its use in CLIA-approved clinical laboratories. CSF concentrations of these three biomarkers reported using xMAP technology differ from those measured by the most commonly used ELISA, confounding attempts to compare results. To develop a model for converting between xMAP and ELISA levels of the three biomarkers, we analyzed CSF samples from 140 subjects (59 AD, 30 controls, 34 with mild cognitive impairment, and 17 with Parkinson's disease, including 1 with dementia). Log-transformation of ELISA and xMAP levels made the variance constant in all three biomarkers and improved the linear regression: t-tau concentrations were highly correlated (r = 0.94); p-tau(181) concentrations by ELISA can be better predicted using both the t-tau and p-tau(181) xMAP values (r = 0.96) as compared to p-tau(181) concentrations alone (r = 0.82); correlation of Aβ(1-42) concentrations was relatively weaker but still high (r = 0.77). Among all six protein/assay combinations, xMAP Aβ(1-42) had the best accuracy for diagnostic classification (88%) between AD and control subjects. In conclusion, our study demonstrates that multiplex xMAP is an appropriate assay platform providing results that can be correlated with research-based ELISA values, facilitating the incorporation of this diagnostic biomarker into routine clinical practice.
阿尔茨海默病（AD）研究最充分的生物标志物是与病理相关的脑脊液（CSF）蛋白淀粉样蛋白-β 42（Aβ（1-42））、总tau（t-tau）和磷酸化氨基酸 181 的 tau（p-tau（181））。许多实验室使用酶联免疫吸附测定（ELISA）测量这些蛋白质。多重 xMAP Luminex 是一种半自动测定平台，具有较小的样本内变异，这可能使其更容易在获得 CLIA 批准的临床实验室中使用。使用 xMAP 技术报告的这些三种生物标志物的 CSF 浓度与最常用的 ELISA 测量的浓度不同，这使得比较结果变得复杂。为了建立一种在 xMAP 和 ELISA 两种方法之间转换这三种生物标志物水平的模型，我们分析了来自 140 名受试者的 CSF 样本（59 名 AD、30 名对照、34 名轻度认知障碍和 17 名帕金森病，包括 1 名痴呆症）。ELISA 和 xMAP 水平的对数转换使所有三种生物标志物的方差保持一致，并改善了线性回归：t-tau 浓度高度相关（r = 0.94）；与单独使用 p-tau（181）浓度（r = 0.82）相比，通过 ELISA 测量的 p-tau（181）浓度可以更好地通过 t-tau 和 p-tau（181）xMAP 值进行预测（r = 0.96）；Aβ（1-42）浓度的相关性虽然相对较弱，但仍然很高（r = 0.77）。在所有六种蛋白质/测定组合中，xMAP Aβ（1-42）在 AD 和对照组之间的诊断分类中具有最佳的准确性（88%）。总之，我们的研究表明，多重 xMAP 是一种合适的测定平台，可提供与研究型 ELISA 值相关的结果，有助于将这种诊断生物标志物纳入常规临床实践。
