Abstract:

Objective: To explore the diagnostic value of cerebrospinal fluid (CSF) biomarkers, total tau protein (t-tau), phosphorylated tau protein 181 (p-tau181) and real-time quaking-induced conversion (RT-QuIC) in sporadic Creutzfeldt-Jakob disease (sCJD). Methods: A retrospective study was conducted on 30 patients diagnosed with probable sCJD at Huashan Hospital, Fudan University from April 2020 to November 2022, serving as the sCJD group. Meanwhile, 25 patients diagnosed with rapidly progressive Alzheimer's disease (AD) and 23 patients diagnosed with autoimmune encephalitis (AE), matched for gender and age with the sCJD group, were selected as the AD group and AE group, respectively. CSF t- tau, p-tau181 and t- tau/p-tau181 ratio were collected from the 3 groups. The auxiliary examination data of the sCJD group, including typical manifestations of electroencephalography (EEG) and head MRI, as well as RT- QuIC results, were collected with emphasis. Results: There were statistically significant differences in CSF t-tau (χ² = 38.247, P = 0.000), p-tau181 (χ² = 22.855, P = 0.000) and t-tau/p-tau181 ratio (χ² = 43.780, P = 0.000) among 3 groups. Further pairwise comparisons revealed that the t- tau in the sCJD group was higher than that in the AD group (Z =-4.392, P = 0.000) and AE group (Z =-5.852, P = 0.000); the p-tau181 in the AD group was higher than that in the sCJD group (Z = 2.830, P = 0.014) and AE group (Z = 4.758, P = 0.000); the t-tau/p-tau181 ratio in the sCJD group was higher than that in the AD group (Z =-6.601, P = 0.000) and AE group (Z =-3.339, P = 0.003), and the t-tau/p-tau181 ratio in the AE group was higher than that in the AD group (Z =-2.984, P = 0.009). Among the 30 patients in the sCJD group, 70% (21/30) exhibited abnormal MRI findings in the brain, all displaying the typical cortical "lace sign"; 40% (12/30) showed typical triphasic waves on EEG. In the sCJD group, 7 cases underwent CSF RT-QuIC, and pathogenic prion protein was detected in 5 patients. Conclusions: Elevated CSF t-tau and t-tau/p-tau181 ratio, as well as positive RT-QuIC results, hold certain diagnostic value for sCJD.

Key words: Creutzfeldt-Jakob syndrome, Alzheimer disease, Encephalitis, Autoimmune diseases, Biomarkers, Diagnosis

摘要：

目的: 探讨脑脊液生物学标志物总tau蛋白(t-tau)和磷酸化tau蛋白181(p-tau181)及实时震动诱导转化(RT-QuIC)在散发型克-雅病(sCJD)中的诊断价值。方法: 共纳入2020年4月至2022年11月复旦大学附属华山医院收治的30例很可能的散发型克-雅病患者(sCJD组)，同时选择性别、年龄与其相匹配的出院时诊断为快速进展性阿尔茨海默病的25例患者(AD组)及自身免疫性脑炎的23例患者(AE组)。收集3组患者脑脊液t-tau、p-tau181、t-tau/p-tau181比值；重点收集sCJD组患者脑电图、头部MRI及RT-QuIC检测结果。结果: 3组患者脑脊液t-tau(χ²=38.247，P=0.000)、p-tau181(χ²=22.855，P=0.000)和t-tau/p-tau181比值(χ²=43.780，P=0.000)差异均具有统计学意义，其中sCJD组t-tau高于AD组(Z=-4.392，P=0.000)和AE组(Z=-5.852，P=0.000)；AD组p-tau181高于sCJD组(Z=2.830，P=0.014)和AE组(Z=4.758，P=0.000)；sCJD组t-tau/p-tau181比值高于AD组(Z=-6.601，P=0.000)和AE组(Z=-3.339，P=0.003)，AE组亦高于AD组(Z=-2.984，P=0.009)。sCJD组有70%(21/30)患者头部MRI存在典型皮质“花边征”；40%(12/30)患者脑电图存在典型三相波；7例行脑脊液RT-QuIC检测，5例检出致病性朊病毒。结论: 脑脊液t-tau、t-tau/p-tau181比值升高及RT-QuIC检测阳性对散发型克-雅病具有一定诊断价值。

关键词: 克-亚综合征, 阿尔茨海默病, 脑炎, 自身免疫疾病, 生物标记, 诊断