Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, University of Antwerp, Antwerp, Belgium.
J Alzheimers Dis. 2013;33(1):117-31. doi: 10.3233/JAD-2012-121246.
Combined analysis of the Alzheimer's disease (AD) biomarkers amyloid-β(1-42) (Aβ(1-42)), total tau (T-tau), and hyperphosphorylated tau (P-tau(181P)) in cerebrospinal fluid (CSF) reduces the uncertainty associated with clinical dementia diagnosis. The present study evaluated the diagnostic accuracy of the CSF biomarker concentrations obtained with a multi-analyte Luminex assay (INNO-BIA AlzBio3) in comparison to single-analyte ELISA tests (INNOTEST). Data from 66 pathologically-confirmed dementia patients (51 AD and 15 non-AD) and 95 controls were included. Cut-off values were determined for each individual biomarker determined using both methods for different diagnostic challenges (dementia-controls; AD-controls; AD-non-AD). Comparing the diagnostic accuracy of individual cut-off values between INNO-BIA and INNOTEST, no relevant differences could be identified. Logistic regression was used in addition to identify the best combination of predictor variables (biomarkers). Discrimination of dementia patients from controls using Aβ(1-42) and T-tau yielded a diagnostic accuracy of 0.87 and 0.90 for INNO-BIA and INNOTEST, respectively. Discriminating AD patients from controls, the diagnostic accuracy was 0.90 and 0.93 for INNO-BIA and INNOTEST, respectively. Optimal discrimination of AD and non-AD patients was achieved by combining Aβ(1-42) and P-tau(181P) (diagnostic accuracy = 0.86). In conclusion, which AD biomarkers or combination thereof are most informative is dependent on the differential diagnosis, but the clinical value of these markers in each of the differential diagnoses is independent of the method by which concentrations are determined. Since the clinical value of the ELISA (INNOTEST) and Luminex (INNO-BIA) tests is comparable, further research to select the most suitable analytical platform for routine CSF biomarker measurements is needed.
阿尔茨海默病（AD）生物标志物淀粉样蛋白-β（1-42）（Aβ（1-42））、总tau（T-tau）和磷酸化 tau（P-tau（181P））在脑脊液（CSF）中的联合分析降低了与临床痴呆诊断相关的不确定性。本研究评估了与单分析物 ELISA 测试（INNOTEST）相比，CSF 生物标志物浓度的多分析物 Luminex 分析（INNO-BIA AlzBio3）获得的诊断准确性。纳入了 66 例经病理证实的痴呆患者（51 例 AD 和 15 例非 AD）和 95 例对照。使用两种方法为不同的诊断挑战（痴呆对照；AD 对照；AD-非 AD）确定了每个单独生物标志物的截止值。比较 INNO-BIA 和 INNOTEST 之间单个截止值的诊断准确性，未发现明显差异。除了识别预测变量（生物标志物）的最佳组合外，还使用逻辑回归。使用 Aβ（1-42）和 T-tau 从对照中区分痴呆患者，INNO-BIA 和 INNOTEST 的诊断准确性分别为 0.87 和 0.90。从对照中区分 AD 患者，INNO-BIA 和 INNOTEST 的诊断准确性分别为 0.90 和 0.93。通过组合 Aβ（1-42）和 P-tau（181P）可实现 AD 和非 AD 患者的最佳区分（诊断准确性=0.86）。总之，哪些 AD 生物标志物或其组合最具信息量取决于鉴别诊断，但这些标志物在每种鉴别诊断中的临床价值与确定浓度的方法无关。由于 ELISA（INNOTEST）和 Luminex（INNO-BIA）测试的临床价值相当，因此需要进一步研究以选择最适合常规 CSF 生物标志物测量的分析平台。
