Supplementary Material for: Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs

<b><i>Background:</i></b> Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions. <b><i>Methods:</i></b> We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs. Additionally, the correlation between biomarkers and disease duration as well as the influence of the PRNP129 polymorphism are reported. <b><i>Results:</i></b> The tau levels and p-tau/tau ratios differed considerably between sCJD and clinically characterized non-CJD cases (<i>p</i> &lt; 0.001). p-tau was only elevated in sCJD when compared to cases without dementia (<i>p</i> &lt; 0.05). Tau and the p-tau/tau ratio showed a sensitivity of 95 and 100%, respectively, in detecting sCJD cases. A negative correlation between tau levels and disease duration, but not the timing of lumbar puncture was observed. <b><i>Conclusion:</i></b> The present findings confirmed the value of the p-tau/tau ratio as a robust sCJD biomarker and suggest a role for tau as prognostic marker.

<b><i>背景：</i></b> 已有多项生物标志物被提出，用于区分散发性克雅氏病（sporadic Creutzfeldt-Jakob disease, sCJD）与其他痴呆症及对照个体。然而，这些标志物的临床准确性依赖于PRNP密码子129基因型，目前尚不明确已确立的标志物在未被检测过的人群中表现如何。
<b><i>方法：</i></b> 本研究对波兰多家医院收集的人群样本中的14-3-3蛋白、tau蛋白、磷酸化tau蛋白（phosphorylated tau, p-tau）水平以及p-tau/tau比值进行了分析，样本涵盖非痴呆症患者、痴呆症患者以及确诊的散发性克雅氏病病例，并依据此前确立的临界值对各项参数进行了验证。此外，本研究还报告了生物标志物与疾病病程之间的相关性，以及PRNP129多态性的影响。
<b><i>结果：</i></b> 散发性克雅氏病患者与经临床表征的非克雅氏病患者之间，tau蛋白水平及p-tau/tau比值存在显著差异（p < 0.001）。相较于无痴呆症的病例，仅在散发性克雅氏病患者中观察到p-tau水平升高（p < 0.05）。在检测散发性克雅氏病病例时，tau蛋白及p-tau/tau比值的诊断灵敏度分别达到95%与100%。本研究还发现，tau蛋白水平与疾病病程呈负相关，但与腰椎穿刺的时间无明显关联。
<b><i>结论：</i></b> 本研究结果证实了p-tau/tau比值作为可靠的散发性克雅氏病生物标志物的价值，并提示tau蛋白可作为预后标志物。