Reference Center for Biological Markers of Dementia, Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Alzheimers Res Ther. 2017 Jul 14;9(1):49. doi: 10.1186/s13195-017-0275-5.
The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ, t-tau, and p-tau overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis.
The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ, t-tau, p-tau, and p-tau were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests.
The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau when differentiating between AD or non-AD dementias and controls.
The addition of p-tau to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.
阿尔茨海默病（AD）的脑脊液（CSF）生物标志物 Aβ、t-tau 和 p-tau 与其他疾病重叠。新的 tau 修饰或表位，如非磷酸化 tau 片段（p-tau），可能会改善鉴别痴呆症的诊断。本研究的目的是研究 p-tau 是否可以提高 AD CSF 生物标志物组合用于鉴别痴呆症诊断的诊断性能。
研究人群包括 45 例 AD、45 例额颞叶变性（FTLD）、45 例路易体痴呆（DLB）和 21 例克雅氏病（CJD）患者，以及 20 名认知健康对照者。患者中有相当一部分是经病理证实的。使用市售的单分析物酶联免疫吸附测定（ELISA）试剂盒测定 CSF 中的 Aβ、t-tau、p-tau 和 p-tau 水平。通过接收者操作特征（ROC）曲线分析评估诊断性能，并使用 DeLong 检验比较曲线下面积（AUC）值。
确定了每种不同痴呆症组与对照组之间的两两比较的单个标志物以及生物标志物比值的诊断性能。当将 p-tau 添加到 AD 生物标志物组合中时，其区分非 AD、FTLD 和 DLB 与 AD 的诊断性能降低。作为单一标志物，p-tau 增加了 CJD 的诊断性能。当区分 AD 或非 AD 痴呆症与对照组时，添加 p-tau 并未导致 AUC 值有显著差异。
将 p-tau 添加到 AD CSF 生物标志物组合中未能改善 AD 与非 AD 痴呆症之间的区分。
