Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases
Background and purposeCalmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF C...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1341886/full |
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| author | Xiao-Xi Jia Chao Hu Chao Hu Cao Chen Cao Chen Li-Ping Gao Dong-Lin Liang Wei Zhou Run-Dong Cao Kang Xiao Qi Shi Qi Shi Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong |
| author_facet | Xiao-Xi Jia Chao Hu Chao Hu Cao Chen Cao Chen Li-Ping Gao Dong-Lin Liang Wei Zhou Run-Dong Cao Kang Xiao Qi Shi Qi Shi Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong |
| author_sort | Xiao-Xi Jia |
| collection | DOAJ |
| description | Background and purposeCalmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs.MethodsA total of 103 CSF samples from patients diagnosed with T188K-gCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzyme-linked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors.ResultsThe positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients.ConclusionWestern blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF. |
| first_indexed | 2024-03-08T04:51:40Z |
| format | Article |
| id | doaj.art-7507483d34d648849fd0eb63124a1a6f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-03-08T04:51:40Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-7507483d34d648849fd0eb63124a1a6f2024-02-08T04:29:51ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-02-011710.3389/fnmol.2024.13418861341886Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseasesXiao-Xi Jia0Chao Hu1Chao Hu2Cao Chen3Cao Chen4Li-Ping Gao5Dong-Lin Liang6Wei Zhou7Run-Dong Cao8Kang Xiao9Qi Shi10Qi Shi11Xiao-Ping Dong12Xiao-Ping Dong13Xiao-Ping Dong14Xiao-Ping Dong15National Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaXuanwu Hospital Capital Medical University, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaCenter for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaChina Academy of Chinese Medical Sciences, Beijing, ChinaNational Key-Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaCenter for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, ChinaChina Academy of Chinese Medical Sciences, Beijing, ChinaShanghai Institute of Infectious Disease and Biosafety, Shanghai, ChinaBackground and purposeCalmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs.MethodsA total of 103 CSF samples from patients diagnosed with T188K-gCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzyme-linked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors.ResultsThe positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients.ConclusionWestern blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1341886/fullgenetic prion diseasescerebrospinal fluidcalmodulintau14-3-3 |
| spellingShingle | Xiao-Xi Jia Chao Hu Chao Hu Cao Chen Cao Chen Li-Ping Gao Dong-Lin Liang Wei Zhou Run-Dong Cao Kang Xiao Qi Shi Qi Shi Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong Xiao-Ping Dong Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases Frontiers in Molecular Neuroscience genetic prion diseases cerebrospinal fluid calmodulin tau 14-3-3 |
| title | Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases |
| title_full | Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases |
| title_fullStr | Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases |
| title_full_unstemmed | Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases |
| title_short | Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases |
| title_sort | different reactive profiles of calmodulin in the csf samples of chinese patients of four types of genetic prion diseases |
| topic | genetic prion diseases cerebrospinal fluid calmodulin tau 14-3-3 |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2024.1341886/full |
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