β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease
Abstract Background 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). Methods We analyzed 314 CSF sample...
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2025-02-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01688-9 |
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| author | Bing Xu Kang Xiao Xiaoxi Jia Rundong Cao Donglin Liang Ruhan A Weiwei Zhang Chunjie Li Liping Gao Cao Chen Qi Shi Xiaoping Dong |
| author_facet | Bing Xu Kang Xiao Xiaoxi Jia Rundong Cao Donglin Liang Ruhan A Weiwei Zhang Chunjie Li Liping Gao Cao Chen Qi Shi Xiaoping Dong |
| author_sort | Bing Xu |
| collection | DOAJ |
| description | Abstract Background 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). Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-716d25cd1ef8463fa826a10e82e664a2 |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-716d25cd1ef8463fa826a10e82e664a22025-02-09T12:16:12ZengBMCAlzheimer’s Research & Therapy1758-91932025-02-011711910.1186/s13195-025-01688-9β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s diseaseBing Xu0Kang Xiao1Xiaoxi Jia2Rundong Cao3Donglin Liang4Ruhan A5Weiwei Zhang6Chunjie Li7Liping Gao8Cao Chen9Qi Shi10Xiaoping Dong11National 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionNational 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 PreventionAbstract Background 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). Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s13195-025-01688-9β-synucleinCerebrospinal fluidHuman prion diseases |
| spellingShingle | Bing Xu Kang Xiao Xiaoxi Jia Rundong Cao Donglin Liang Ruhan A Weiwei Zhang Chunjie Li Liping Gao Cao Chen Qi Shi Xiaoping Dong β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease Alzheimer’s Research & Therapy β-synuclein Cerebrospinal fluid Human prion diseases |
| title | β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease |
| title_full | β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease |
| title_fullStr | β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease |
| title_full_unstemmed | β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease |
| title_short | β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer’s and Parkinson’s disease |
| title_sort | β synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from alzheimer s and parkinson s disease |
| topic | β-synuclein Cerebrospinal fluid Human prion diseases |
| url | https://doi.org/10.1186/s13195-025-01688-9 |
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