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磷酸化 tau 181(p-tau)作为一种创新的、快速且稳健的脑脊液漏的生物标志物。

Phosphorylated tau 181 (p-tau) as an innovative, fast and robust biomarker for cerebrospinal fluid leaks.

机构信息

Department of Laboratory Medicine, Clinique Saint-Pierre, 1340, Ottignies, Belgium.

Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

出版信息

J Neurol. 2024 Oct;271(10):6724-6728. doi: 10.1007/s00415-024-12624-6. Epub 2024 Aug 20.

Abstract

BACKGROUND

Cerebrospinal fluid (CSF) leaks can lead to serious complications if left untreated, making rapid and accurate diagnosis essential. Biomarkers such as β2-transferrin (B2TRF) and β-trace protein are used to detect CSF leaks, but their limitations warrant the exploration of alternative markers. This study investigates the potential of phosphorylated tau at threonine 181 (p-tau) as a biomarker for CSF leaks.

METHODS

Samples from 56 subjects were analyzed for B2TRF and p-tau using immunoaffinity blotting and chemiluminescent enzyme immunoassay, respectively. Data analysis included Mann-Whitney test to assess the overall difference in median p-tau concentrations between B2TRF positive and negative patients and a receiver operating characteristic (ROC) curve analysis to determine optimal p-tau cutoff values for predicting B2TRF positivity.

RESULTS

p-tau levels were significantly higher in B2TRF positive samples compared to negative samples (p < 0.001). ROC analysis showed high diagnostic performance for p-tau, with an optimal cutoff of 13.22 pg/mL providing 92.0% sensitivity and 93.1% specificity. Excluding hemolyzed samples improved further the diagnostic performances, maintaining high sensitivity (90.9%) and achieving perfect specificity (100.0%).

CONCLUSIONS

This study highlights the potential of p-tau as a valuable biomarker for the detection of CSF leaks due to its high diagnostic accuracy and practical advantages over the current biomarkers. The characteristics of p-tau assay being both quantitative and rapid, with high diagnostic accuracy, suggest that it could be a valuable tool for the detection of CSF leaks. Further research are now needed to validate these findings.

摘要

背景

如果不加以治疗,脑脊液(CSF)泄漏会导致严重的并发症,因此快速准确的诊断至关重要。β2-转铁蛋白(B2TRF)和β-痕迹蛋白等生物标志物被用于检测 CSF 泄漏,但它们的局限性需要探索替代标志物。本研究探讨了磷酸化 tau 丝氨酸 181 位(p-tau)作为 CSF 泄漏标志物的潜力。

方法

使用免疫亲和印迹法分析 56 例样本中的 B2TRF,使用化学发光酶免疫分析法分析 p-tau。数据分析包括 Mann-Whitney 检验评估 B2TRF 阳性和阴性患者之间 p-tau 浓度中位数的总体差异,以及接受者操作特征(ROC)曲线分析确定预测 B2TRF 阳性的最佳 p-tau 截断值。

结果

B2TRF 阳性样本的 p-tau 水平明显高于阴性样本(p<0.001)。ROC 分析显示 p-tau 的诊断性能较高,最佳截断值为 13.22pg/mL,具有 92.0%的灵敏度和 93.1%的特异性。排除溶血样本进一步提高了诊断性能,保持了 90.9%的高灵敏度和 100.0%的完美特异性。

结论

本研究强调了 p-tau 作为 CSF 泄漏检测的有价值的生物标志物的潜力,因为其具有较高的诊断准确性和相对于当前生物标志物的实际优势。p-tau 检测具有定量和快速的特点,诊断准确性高,这表明它可能是 CSF 泄漏检测的有价值工具。现在需要进一步研究来验证这些发现。

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