Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease Results From the Swedish Mortality Registry
Diagnostic Performance of Cerebrospinal Fluid Total Tau and Phosphorylated Tau in Creutzfeldt-Jakob Disease Results From the Swedish Mortality Registry
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DOI：
10.1001/jamaneurol.2013.6455
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发表时间：
2014-04-01
期刊：
影响因子：
29
通讯作者：
Zetterberg, Henrik
中科院分区：
文献类型：
--
作者：
Skillback, Tobias;Rosen, Christoffer;Zetterberg, Henrik
目的通过分析大量常规临床样本数据库的结果，结合瑞典死亡率登记处的诊断信息，测试痴呆脑脊液生物标记物总tau(T-tau)、磷酸化tau(P-tau)和T-tau/P-tau的诊断性能，以测试痴呆脑脊液(CSF)生物标记物的诊断性能。我们用瑞典Sahlgrenska大学医院临床神经化学实验室的常规临床测试中进行的T-tau和P-tau的脑脊液测量数据集交叉参考了瑞典死亡率登记处，该医院为瑞典大部分地区提供服务。数据集包括9765例接受脑脊液检查的已故患者，其中93例为CJD，52例尸检样本(56%)。主要测量结果和每个患者的脑脊液中T-tau和P-tau水平，并计算T-tau/P-tau比率。分析生物标记物水平(根据年龄和性别进行调整)与记录的死亡原因和死亡时间的关系。我们专门测试了先前定义的CJD生物标志物(T-tau>；1400 ng/gt；1400 ng/gt；和T-tau/P-tau-Ratio>；25)。结果与死于阿尔茨海默病(AD)和其他痴呆的患者相比，死于CJD的患者脑脊液T-tau水平和T-tau/P-tau比值升高，但脑脊液P-tau水平没有升高。先前定义的生物标志物图谱的特异度为99.0%，敏感度为78.5%，阳性似然比为79.9。当与常见的鉴别诊断进行比较时，该图谱对AD的敏感性、特异性和阳性似然比分别为78.5%、99.6%和196.6，而对其他痴呆的敏感性、特异性和阳性似然比分别为78.5%、99.3%和109.3。在反复测量的CJD患者(n=30)中，但在AD(n=242)或其他痴呆患者(n=258)中，T-tau水平和T-tau/P-tau比率随着时间的推移而增加。结论在这一常规临床环境中，CJD患者T-tau水平升高和T-tau/P-tau比率升高对CJD的重要鉴别诊断具有非常高的特异性，可作为临床有用的诊断试验。
IMPORTANCE Identifying a clinical distinction between the invariably lethal prion disease Creutzfeldt-Jakob disease (CJD) and nonprion rapidly progressive dementias is important and sometimes difficult; thus, reliable tools for diagnosis are in great demand.OBJECTIVE To test the diagnostic performance of dementia cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and the T-tau to P-tau ratio for CJD by analyzing the results from a large database of routine clinical samples in combination with diagnosis information from the Swedish Mortality Registry.DESIGN, SETTING, AND PARTICIPANTS This was a retrospective cohort study. We cross-referenced the Swedish Mortality Registry with a data set of CSF measurements of T-tau and P-tau performed in routine clinical testing at the Clinical Neurochemistry Laboratory of the Sahlgrenska University Hospital, which serves most of Sweden. The data set consisted of 9765 deceased individuals with CSF measures, including 93 with CJD, with 52 autopsy-verified samples (56%).MAIN OUTCOMES AND MEASURES For each patient, T-tau and P-tau levels in CSF were measured and the T-tau to P-tau ratio was calculated. Biomarker levels (adjusted for age and sex) were analyzed in relation to the recorded cause of death and time of death. We specifically tested a previously defined CJD biomarker profile (T-tau >1400 ng/L and T-tau to P-tau-ratio >25).RESULTS Patients who died of CJD had elevated CSF T-tau levels and T-tau to P-tau ratio, but not elevated CSF P-tau levels, compared with patients who died of Alzheimer disease (AD) and other dementias. The previously defined biomarker profile had a specificity of 99.0%, a sensitivity of 78.5%, and a positive likelihood ratio of 79.9. When tested against common differential diagnoses, the sensitivity, specificity, and positive likelihood ratio of this profile was 78.5%, 99.6%, and 196.6, respectively, in relation to AD and 78.5%, 99.3%, and 109.3, respectively, in relation to other dementias. In CJD individuals (n = 30) with repeated measurements, but not in those with AD (n = 242) or other dementias (n = 258), T-tau levels and T-tau to P-tau ratios increased over time.CONCLUSIONS AND RELEVANCE In this routine clinical setting, the combination of increased T-tau levels and increased T-tau to P-tau ratios in CJD patients has a very high specificity against important differential diagnoses to CJD and may serve as a clinically useful diagnostic test.