Cerebrospinal fluid non-phosphorylated tau in the differential diagnosis of Creutzfeldt–Jakob disease: a comparative prospective study with 14-3-3

被引:0
作者
Franc Llorens
Anna Villar-Piqué
Peter Hermann
Matthias Schmitz
Stefan Goebel
Katharina Waniek
Ingolf Lachmann
Inga Zerr
机构
[1] Network Center for Biomedical Research in Neurodegenerative Diseases,Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance
[2] (CIBERNED),undefined
[3] Institute Carlos III,undefined
[4] University Medical School,undefined
[5] Bellvitge Biomedical Research Institute (IDIBELL),undefined
[6] German Center for Neurodegenerative Diseases (DZNE),undefined
[7] AJ Roboscreen GmbH,undefined
来源
Journal of Neurology | 2020年 / 267卷
关键词
Cerebrospinal fluid; Creutzfeldt–Jakob disease; Tau; Non-phosphorylated tau; 14-3-3; RT-QuIC; Biomarker;
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学科分类号
摘要
Cerebrospinal fluid (CSF) non-phosphorylated tau (non-p-tau) is increased in sporadic Creutzfeldt–Jakob disease (CJD), but its accuracy in the differential diagnosis has not been previously established. Here, we first used a retrospective cohort of non-CJD (n = 135) and CJD (n = 137) cases to determine the optimal cutoff point for the discrimination of CJD cases. Next, we prospectively quantified non-p-tau and 14-3-3 protein in a cohort of 1427 cases received for CSF testing at the German National Reference Center for transmissible spongiform encephalopathies. Among them, 36 were subsequently diagnosed as CJD. The diagnostic accuracy of both proteins discriminating CJD cases was evaluated. Using a cutoff of 650 pg/mL, non-p-tau displayed 94.39% accuracy in discriminating CJD cases, while 92.92% accuracy was achieved by 14-3-3 using a cutoff of 20,000 AU/mL. Diagnostic test evaluation for both proteins showed a slightly better performance of non-p-tau compared to 14-3-3. The two biomarkers’ concentrations showed a significant positive correlation, both in the total population and in CJD cases (p < 0.001). Finally, the analysis of CSF non-p-tau concentrations when undergoing pre-analytical factors showed high stability in front of temperature storage and freeze/thaw cycles. Therefore, we conclude that when used in the appropriate clinical context of a prion disease surveillance center, non-p-tau is a highly sensitive and specific diagnostic marker for CJD.
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页码:543 / 550
页数:7
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