{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:01:48Z","timestamp":1770814908141,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SKLID Development Grants","award":["2021SKLID504"],"award-info":[{"award-number":["2021SKLID504"]}]},{"name":"SKLID Development Grants","award":["2019SKLID401"],"award-info":[{"award-number":["2019SKLID401"]}]},{"name":"SKLID Development Grants","award":["2019SKLID603"],"award-info":[{"award-number":["2019SKLID603"]}]},{"name":"SKLID Development Grants","award":["2021SKLID503"],"award-info":[{"award-number":["2021SKLID503"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growth-associated protein-43 (GAP43) is a neuronal protein essential for synaptic function and plasticity, and its reduction has been observed in brains of prion diseases (PrDs) and rodent models. However, its status in the cerebrospinal fluid (CSF) of patients with PrDs remains unclear. CSF samples from 140 PrD cases, including 48 sCJD, 35 T188K-gCJD, 22 E200K-gCJD, 35 D178N-FFI, and 36 non-PrD controls, were analyzed for GAP43 by Western blot. The results were compared with 14-3-3 and calmodulin (CaM) detected by WB, and associated with clinical features. GAP43 positivity was significantly higher in sCJD (70.83%), T188K-gCJD (65.71%), and E200K-gCJD (72.73%) than in non-PrD controls (27.78%). The sensitivity and specificity of GAP43 (around 70\u201375%) were comparable to 14-3-3 and CaM, though inferior to RT-QuIC and total tau reported elsewhere. CSF GAP43 positivity correlated with sCJD-associated MRI changes, periodic sharp-wave complexes (PSWC) on EEG, and with 14-3-3 and CaM positivity. Our data here indicate the feasibility of usage of GAP43 by Western blot analysis as a diagnostic, at least as a screening, biomarker for sCJD and certain types of gPrDs.<\/jats:p>","DOI":"10.3390\/ijms27041678","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T14:05:15Z","timestamp":1770645915000},"page":"1678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Proportions of GAP43 Positivity in the Cerebrospinal Fluids of Patients with Sporadic and Certain Types of Genetic Creutzfeldt-Jakob Diseases by Western Blot Analysis"],"prefix":"10.3390","volume":"27","author":[{"given":"Xiao-Xi","family":"Jia","sequence":"first","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Hu","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Feng","family":"Zeng","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Xu","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Zheng","family":"Li","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru-Han","family":"A","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Lin","family":"Liang","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run-Dong","family":"Cao","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-0418","authenticated-orcid":false,"given":"Li-Ping","family":"Gao","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-9283","authenticated-orcid":false,"given":"Cao","family":"Chen","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-8447","authenticated-orcid":false,"given":"Xiao-Ping","family":"Dong","sequence":"additional","affiliation":[{"name":"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 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1212\/01.WNL.0000160117.56690.B2","article-title":"Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada","volume":"64","author":"Ladogana","year":"2005","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/ije\/31.2.490","article-title":"Analysis of the geographical distribution of sporadic Creutzfeldt-Jakob disease in France between 1992 and 1998","volume":"31","author":"Cousens","year":"2002","journal-title":"Int. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"322ra9","DOI":"10.1126\/scitranslmed.aad5169","article-title":"Quantifying prion disease penetrance using large population control cohorts","volume":"8","author":"Minikel","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3346\/jkms.2014.29.5.623","article-title":"Genetic studies in human prion diseases","volume":"29","author":"Jeong","year":"2014","journal-title":"J. Korean Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"901","DOI":"10.3201\/eid1806.120116","article-title":"Iatrogenic Creutzfeldt-Jakob disease, final assessment","volume":"18","author":"Brown","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0140-6736(96)91412-9","article-title":"A new variant of Creutzfeldt-Jakob disease in the UK","volume":"347","author":"Will","year":"1996","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1016\/S0140-6736(06)68930-7","article-title":"Kuru in the 21st century\u2014An acquired human prion disease with very long incubation periods","volume":"367","author":"Collinge","year":"2006","journal-title":"Lancet"},{"key":"ref_8","unstructured":"(2025, February 04). CDC\u2019s Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD). Centers for Disease Control and Prevention, Atlanta, GA, Available online: https:\/\/www.cdc.gov\/creutzfeldt-jakob\/hcp\/clinical-overview\/?CDC_AAref_Val=."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1212\/WNL.0000000000005860","article-title":"Validation and utilization of amended diagnostic criteria in Creutzfeldt-Jakob disease surveillance","volume":"91","author":"Hermann","year":"2018","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1474-4422(20)30477-4","article-title":"Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease","volume":"20","author":"Hermann","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1111\/ene.14655","article-title":"Calmodulin level is significantly increased in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease","volume":"28","author":"Chen","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jia, X.X., Hu, C., Chen, C., Gao, L.P., Liang, D.L., Zhou, W., Cao, R.D., Xiao, K., Shi, Q., and Dong, X.P. (2024). Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases. Front. Mol. Neurosci., 17.","DOI":"10.3389\/fnmol.2024.1341886"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1434","DOI":"10.1212\/WNL.0000000000200002","article-title":"Blood beta-Synuclein and Neurofilament Light Chain During the Course of Prion Disease","volume":"98","author":"Halbgebauer","year":"2022","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s12035-014-8758-x","article-title":"Analyses of the similarity and difference of global gene expression profiles in cortex regions of three neurodegenerative diseases: Sporadic Creutzfeldt-Jakob disease (sCJD), fatal familial insomnia (FFI), and Alzheimer\u2019s disease (AD)","volume":"50","author":"Tian","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3892\/ijmm.2013.1239","article-title":"Global transcriptional profiling of the postmortem brain of a patient with G114V genetic Creutzfeldt-Jakob disease","volume":"31","author":"Tian","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.neuroscience.2004.03.060","article-title":"Subfield-specific increase in brain growth protein in postmortem hippocampus of Alzheimer\u2019s patients","volume":"126","author":"Rekart","year":"2004","journal-title":"Neuroscience"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Xiao, K., Yang, X., Zhou, W., Chen, C., Shi, Q., and Dong, X. (2021). Validation and Application of Skin RT-QuIC to Patients in China with Probable CJD. Pathogens, 10.","DOI":"10.3390\/pathogens10121642"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/jnnp-2022-330153","article-title":"Evaluation of the impact of CSF prion RT-QuIC and amended criteria on the clinical diagnosis of Creutzfeldt-Jakob disease: A 10-year study in Italy","volume":"94","author":"Mastrangelo","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1007\/s12264-021-00764-y","article-title":"Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease","volume":"37","author":"Shi","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.18632\/oncotarget.13998","article-title":"Progress in CSF biomarker discovery in sCJD","volume":"8","author":"Llorens","year":"2017","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/acn3.304","article-title":"Biomarkers for sporadic Creutzfeldt-Jakob disease","volume":"3","author":"Soomro","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1074\/mcp.M116.059915","article-title":"Alpha-, Beta-, and Gamma-synuclein Quantification in Cerebrospinal Fluid by Multiple Reaction Monitoring Reveals Increased Concentrations in Alzheimer\u2019s and Creutzfeldt-Jakob Disease but No Alteration in Synucleinopathies","volume":"15","author":"Oeckl","year":"2016","journal-title":"Mol. Cell Proteomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1177271920950319","DOI":"10.1177\/1177271920950319","article-title":"Fluid Biomarkers for Synaptic Dysfunction and Loss","volume":"15","author":"Camporesi","year":"2020","journal-title":"Biomark. Insights"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.meegid.2012.11.019","article-title":"Clinical and familial characteristics of eight Chinese patients with T188K genetic Creutzfeldt-Jakob disease","volume":"14","author":"Chen","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/s41598-019-38520-y","article-title":"The genetic Creutzfeldt-Jakob disease with E200K mutation: Analysis of clinical, genetic and laboratory features of 30 Chinese patients","volume":"9","author":"Gao","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, C., Hu, C., Shi, Q., Zhou, W., Xiao, K., Wang, Y., Liu, L., Chen, J., Xia, Y., and Dong, X.P. (2019). Profiles of 14-3-3 and Total Tau in CSF Samples of Chinese Patients of Different Genetic Prion Diseases. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00934"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/19336896.2019.1617027","article-title":"Clinical features and genetic characteristics of two Chinese pedigrees with fatal family insomnia","volume":"13","author":"He","year":"2019","journal-title":"Prion"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Holahan, M.R. (2017). A Shift from a Pivotal to Supporting Role for the Growth-Associated Protein (GAP-43) in the Coordination of Axonal Structural and Functional Plasticity. Front. Cell Neurosci., 11.","DOI":"10.3389\/fncel.2017.00266"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1212\/WNL.56.1.127","article-title":"Altered expression of synaptic proteins occurs early during progression of Alzheimer\u2019s disease","volume":"56","author":"Masliah","year":"2001","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E4016","DOI":"10.1073\/pnas.1309143110","article-title":"Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model","volume":"110","author":"Janezic","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1007\/s12035-024-04568-9","article-title":"Aberrance of GAP43\/p-GAP43 Closely Associates with the Pathology of Neuron Loss in Prion-Infected Rodent Models","volume":"62","author":"Jia","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/neup.12355","article-title":"Creutzfeldt-Jakob disease","volume":"37","author":"Iwasaki","year":"2017","journal-title":"Neuropathology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/(SICI)1097-4547(19991001)58:1<107::AID-JNR11>3.0.CO;2-G","article-title":"Homeostatic tuning of Ca2+ signal transduction by members of the calpacitin protein family","volume":"58","author":"Gerendasy","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_34","unstructured":"(2017). Creutzfeldt-Jakob Disease Diagnosis (Standard No. WS\/T 562-2017)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:19:27Z","timestamp":1770801567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041678"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041678","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}