Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP
Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP
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DOI：
10.1212/01.wnl.0000436625.63650.27
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发表时间：
2013-11-26
期刊：
影响因子：
9.9
通讯作者：
Levey, Allan I.
中科院分区：
文献类型：
--
作者：
Hu, William T.;Watts, Kelly;Levey, Allan I.
目的：验证候选CSF生物标志物区分2种主要形式的额颞叶变性（FTLD）、伴有TAR DNA结合蛋白43（TDP-43）包涵体的FTLD的能力（FTLD-TDP）和含Tau夹杂物的FTLD方法：在单中心验证队列中，从30名FTLD患者中采集死前CSF样本，使用独立的测定法测量5种推定的FTLD-TDP生物标志物的CSF水平以及总Tau（t-Tau）和在苏氨酸181处磷酸化的Tau（p-Tau（181））的水平。然后在由FTLD-TDP、FTLD-Tau、阿尔茨海默病（AD）受试者和认知正常受试者组成的单独的2中心验证队列中测试与FTLD-TDP最相关的生物标志物。结果：在第一个验证队列中，FTLD-TDP病例的p-Tau（181）和白细胞介素-23水平降低，Fas水平升高。降低的p-Tau（181）与t-Tau（p/t-Tau）的比率是FTLD-TDP病理学的最强预测因子。第二个验证队列中的分析显示CSF p/t-Tau比值
Objectives: To validate the ability of candidate CSF biomarkers to distinguish between the 2 main forms of frontotemporal lobar degeneration (FTLD), FTLD with TAR DNA-binding protein 43 (TDP-43) inclusions (FTLD-TDP) and FTLD with Tau inclusions (FTLD-Tau).Methods: Antemortem CSF samples were collected from 30 patients with FTLD in a single-center validation cohort, and CSF levels of 5 putative FTLD-TDP biomarkers as well as levels of total Tau (t-Tau) and Tau phosphorylated at threonine 181 (p-Tau(181)) were measured using independent assays. Biomarkers most associated with FTLD-TDP were then tested in a separate 2-center validation cohort composed of subjects with FTLD-TDP, FTLD-Tau, Alzheimer disease (AD), and cognitively normal subjects. The sensitivity and specificity of FTLD-TDP biomarkers were determined.Results: In the first validation cohort, FTLD-TDP cases had decreased levels of p-Tau(181) and interleukin-23, and increased Fas. Reduced ratio of p-Tau(181) to t-Tau (p/t-Tau) was the strongest predictor of FTLD-TDP pathology. Analysis in the second validation cohort showed CSF p/t-Tau ratio