Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease
Association of Blood and Cerebrospinal Fluid Tau Level and Other Biomarkers With Survival Time in Sporadic Creutzfeldt-Jakob Disease
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DOI：
10.1001/jamaneurol.2019.1071
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发表时间：
2019-08-01
期刊：
影响因子：
29
通讯作者：
Geschwind, Michael D.
中科院分区：
文献类型：
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作者：
Staffaroni, Adam M.;Kramer, Abigail O.;Geschwind, Michael D.
要点问题液体生物标志物是否可以超越人口和遗传生物标志物来改善散发性克雅氏病 (sCJD) 的生存时间预测？结果在这项纵向队列研究中，包括 188 名可能或确诊的 sCJD 和密码子 129 基因分型的参与者，除了朊病毒蛋白基因密码子 129 的多态性和基线功能状态外，一些基于脑脊液和血液的生物标志物与 sCJD 患者的生存相关。血液和脑脊液中的总 tau 浓度似乎是最有希望的。意义这项研究提供的证据表明，基于血液的生物标志物可用于预测 sCJD 患者的生存期，从而有可能改善临床护理和我们推动治疗试验的能力。这项纵向队列研究评估血浆和脑脊液生物标志物是否与散发性克雅氏病的生存时间相关。重要性能够预测散发性克雅氏病 (sCJD) 生存时间的液体生物标志物至关重要用于临床护理和治疗试验。目的评估血浆和脑脊液（CSF）生物标志物是否与 sCJD 患者的生存时间相关。设计、背景和参与者在这项纵向队列研究中，收集了 2004 年 3 月至 2018 年 1 月期间转诊至美国三级国家转诊服务的 193 名可能或确诊的 sCJD 患者的数据，这些患者进行了密码子 129 基因分型。对参与者进行评估，直至死亡或在统计分析时进行审查（范围为 0.03-38.3 个月）。我们拟合了 Cox 比例风险模型，并将事件发生时间作为结果。对液体生物标志物进行对数转换，并在有或没有非液体生存生物标志物的情况下运行模型。由于实施了延长生命的措施，五名患者被排除在外。主要结果和指标生存生物标志物包括性别、年龄、密码子 129 基因型、Barthel 指数、医学研究委员会朊病毒疾病评定量表、8 个脑脊液生物标志物（总 tau [t-tau] 水平、磷酸化 tau [p-tau] 水平、t-tau:p-tau 比率、神经丝轻 [NfL] 水平、β-淀粉样蛋白 42 水平、神经元特异性烯醇化酶水平、14-3-3 测试结果和实时震动诱导转化测试）以及 3 种血浆生物标志物（t-tau 水平、NfL 水平和胶质纤维酸性蛋白水平）。结果 188 名参与者中，103 名（54.8%）为男性，平均（SD）年龄为 63.8（9.2）岁。血浆 t-tau 水平（风险比，5.8；95% CI，2.3-14.8；P
Key PointsQuestionCan fluid biomarkers improve prediction of survival time in sporadic Creutzfeldt-Jakob disease (sCJD) above and beyond demographic and genetic biomarkers? FindingsIn this longitudinal cohort study including 188 participants with probable or definite sCJD and codon 129 genotyping, in addition to polymorphisms of prion protein gene codon 129 and baseline functional status, several cerebrospinal fluid-based and blood-based biomarkers were associated with survival in patients with sCJD. Total tau concentrations in the blood and cerebrospinal fluid appear to be the most promising. MeaningThis study provides evidence that blood-based biomarkers can be used to predict survival in patients with sCJD, potentially improving clinical care and our ability to power treatment trials.This longitudinal cohort study assesses whether plasma and cerebrospinal fluid biomarkers are associated with survival time in sporadic Creutzfeldt-Jakob disease.ImportanceFluid biomarkers that can predict survival time in sporadic Creutzfeldt-Jakob disease (sCJD) will be critical for clinical care and for treatment trials. ObjectiveTo assess whether plasma and cerebrospinal fluid (CSF) biomarkers are associated with survival time in patients with sCJD. Design, Setting, and ParticipantsIn this longitudinal cohort study, data from 193 patients with probable or definite sCJD who had codon 129 genotyping referred to a tertiary national referral service in the United States were collected from March 2004 to January 2018. Participants were evaluated until death or censored at the time of statistical analysis (range, 0.03-38.3 months). We fitted Cox proportional hazard models with time to event as the outcome. Fluid biomarkers were log-transformed, and models were run with and without nonfluid biomarkers of survival. Five patients were excluded because life-extending measures were performed. Main Outcomes and MeasuresBiomarkers of survival included sex, age, codon 129 genotype, Barthel Index, Medical Research Council Prion Disease Rating Scale, 8 CSF biomarkers (total tau [t-tau] level, phosphorylated tau [p-tau] level, t-tau:p-tau ratio, neurofilament light [NfL] level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test), and 3 plasma biomarkers (t-tau level, NfL level, and glial fibrillary acidic protein level). ResultsOf the 188 included participants, 103 (54.8%) were male, and the mean (SD) age was 63.8 (9.2) years. Plasma t-tau levels (hazard ratio, 5.8; 95% CI, 2.3-14.8; P