Department of Clinical Chemistry, Neurological Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
Alzheimers Dement. 2013 May;9(3):276-83. doi: 10.1016/j.jalz.2012.01.004. Epub 2012 Oct 27.
Multiplex assays such as xMAP have been proposed for the assessment of Alzheimer's disease (AD) biomarkers amyloid β 42 (Aβ42), tau (Tau), and phosphorylated tau (pTau) in cerebrospinal fluid (CSF). Here, we compared the traditional enzyme-linked immunosorbent assay (ELISA) and xMAP with respect to their: (1) absolute biomarker concentration, (2) ability to distinguish AD from nondemented subjects, (3) ability to monitor AD longitudinally, and (4) ability to predict progression from mild cognitive impairment (MCI) to AD.
We selected 68 AD, 62 MCI, and 24 nondemented subjects, performed clinical examinations, and obtained CSF at baseline and 2 years later. Aβ42, Tau, and pTau were measured with both ELISA and xMAP.
Biomarker levels differed considerably between the two assays, and the differences were concentration dependent. No differences were observed in ability to distinguish nondemented subjects from AD patients between ELISA (area under curve of 0.84 for Aβ42, 0.79 for Tau, and 0.75 for pTau) and xMAP (area under curve of 0.82 for Aβ42, 0.75 for Tau, and 0.73 for pTau), all P < .05. Increased Aβ42 levels of AD patients at follow-up compared with baseline were detected with ELISA, whereas increased Tau levels for nondemented subjects and MCI patients were only detected with xMAP. The hazard ratios for progression from MCI to AD did not differ between the assays.
Both ELISA and multiplex assays can be used to measure AD biomarker levels in CSF to support clinical diagnosis and predict progression from MCI to AD with similar accuracy. Importantly, the assays' output in absolute biomarker concentrations is remarkably different, and this discrepancy cannot be reconciled with simple correction factors.
多重分析，如 xMAP，已被提议用于评估阿尔茨海默病（AD）生物标志物淀粉样蛋白β 42（Aβ42）、tau（Tau）和磷酸化 tau（pTau）在脑脊液（CSF）中的水平。在这里，我们比较了传统的酶联免疫吸附测定（ELISA）和 xMAP，具体涉及以下几个方面：（1）绝对生物标志物浓度；（2）区分 AD 与非痴呆患者的能力；（3）监测 AD 纵向进展的能力；（4）预测从轻度认知障碍（MCI）到 AD 的进展的能力。
我们选择了 68 例 AD、62 例 MCI 和 24 例非痴呆患者，进行临床检查，并在基线和 2 年后获得 CSF。使用 ELISA 和 xMAP 同时测量 Aβ42、Tau 和 pTau。
两种检测方法的生物标志物水平差异很大，且差异与浓度有关。在区分非痴呆患者与 AD 患者方面，ELISA（Aβ42 的曲线下面积为 0.84，Tau 为 0.79，pTau 为 0.75）和 xMAP（Aβ42 的曲线下面积为 0.82，Tau 为 0.75，pTau 为 0.73）之间没有差异，均 P<0.05。ELISA 检测到 AD 患者在随访时的 Aβ42 水平较基线升高，而 xMAP 仅检测到非痴呆患者和 MCI 患者的 Tau 水平升高。从 MCI 到 AD 的进展的危险比在两种检测方法之间没有差异。
ELISA 和多重分析都可用于测量 CSF 中的 AD 生物标志物水平，以支持临床诊断，并以相似的准确性预测从 MCI 到 AD 的进展。重要的是，两种检测方法在绝对生物标志物浓度上的输出结果有很大差异，而且这种差异不能用简单的校正因子来调和。
