Xu Bing, Xiao Kang, Jia Xiaoxi, Cao Rundong, Liang Donglin, A Ruhan, Zhang Weiwei, Li Chunjie, Gao Liping, Chen Cao, Shi Qi, Dong Xiaoping
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Alzheimers Res Ther. 2025 Feb 7;17(1):39. doi: 10.1186/s13195-025-01688-9.
β-synuclein (β-syn), mainly expressed in central nerve system, is one of the biomarkers in cerebrospinal fluid (CSF) and blood for synaptic damage, which has been reported to be elevated in CSF and blood of the patients of prion diseases (PrDs).
We analyzed 314 CSF samples from patients in China National Surveillance for CJD. The diagnostic groups of the 223 patients with PrDs included sporadic Creutzfeldt-Jacob disease (sCJD), genetic CJD (gCJD), fatal familial insomnia (FFI) and Gerstmann-Straussler-Scheinker (GSS). 91 patients with non-PrDs comprised Alzheimer's disease (AD), Parkinson's disease (PD), viral encephalitis (VE) or autoimmune encephalitis (AE) were enrolled in the control groups. The CSF β-syn levels were measured by a commercial microfluidic ELISA. The Mann-Whitney U test and Kruskal-Wallis H test were employed to analyze two or more sets of continuous variables. Multiple linear regression was also performed to evaluate the factors for CSF β-syn levels. Receiver operating characteristics (ROC) curves and area under the curve (AUC) values were used to assess the diagnostic performance of β-syn.
The median of β-syn levels (2074 pg/ml; IQR: 691 to 4332) of all PrDs was significantly higher than that of non-PrDs group (504 pg/ml; IQR: 126 to 3374). The CSF β-syn values in the cohorts of sCJD, T188K-gCJD, E200K-gCJD and P102L-GSS were remarkably higher than that of the group of AD + PD, but similar as that of the group of VE + AE. The elevated CSF β-syn in sCJD and gCJD cases was statistically associated with CSF 14-3-3 positive and appearance of mutism. ROC curve analysis identified satisfied performance for distinguishing from AD + PD, with high AUC values in sCJD (0.7640), T188K-gCJD (0.8489), E200K-gCJD (0.8548), P102L-GSS (0.7689) and D178N-FFI (0.7210), respectively.
Our data here indicate that CSF β-syn is a potential biomarker for distinguishing PrDs (gCJD, sCJD and GSS) from AD and PD, but is much less efficient from VE and AE. These findings have critical implications for early diagnosis and monitoring of synaptic integrity in prion diseases.
β-突触核蛋白（β-syn）主要在中枢神经系统中表达，是脑脊液（CSF）和血液中突触损伤的生物标志物之一，据报道在朊病毒病（PrDs）患者的脑脊液和血液中其水平会升高。
我们分析了中国克雅氏病国家监测项目中患者的314份脑脊液样本。223例PrDs患者的诊断分组包括散发性克雅氏病（sCJD）、遗传性克雅氏病（gCJD）、致死性家族性失眠症（FFI）和格斯特曼-施特劳斯勒-谢inker病（GSS）。91例非PrDs患者组成对照组，包括阿尔茨海默病（AD）、帕金森病（PD）、病毒性脑炎（VE）或自身免疫性脑炎（AE）。通过商业微流控ELISA法检测脑脊液β-syn水平。采用曼-惠特尼U检验和克鲁斯卡尔-沃利斯H检验分析两组或多组连续变量。还进行了多元线性回归以评估脑脊液β-syn水平的影响因素。采用受试者工作特征（ROC）曲线和曲线下面积（AUC）值评估β-syn的诊断性能。
所有PrDs患者β-syn水平的中位数（2074 pg/ml；四分位数间距：691至4332）显著高于非PrDs组（504 pg/ml；四分位数间距：126至3374）。sCJD、T188K-gCJD、E200K-gCJD和P102L-GSS队列中的脑脊液β-syn值显著高于AD + PD组，但与VE + AE组相似。sCJD和gCJD病例中脑脊液β-syn升高与脑脊液14-3-3阳性和缄默的出现具有统计学相关性。ROC曲线分析显示在区分AD + PD方面性能良好，sCJD（0.7640）、T188K-gCJD（0.8489）、E200K-gCJD（0.8548）、P102L-GSS（0.7689）和D178N-FFI（0.7210）的AUC值分别较高。
我们的数据表明，脑脊液β-syn是区分PrDs（gCJD、sCJD和GSS）与AD和PD的潜在生物标志物，但在区分VE和AE方面效率较低。这些发现对朊病毒病的早期诊断和突触完整性监测具有重要意义。
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