{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:33:31Z","timestamp":1770831211865,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Carlos III (Miguel Servet programme) to FL.","award":["CP\/00041"],"award-info":[{"award-number":["CP\/00041"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt\u2013Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked immunosorbent assay in a cohort of rare genetic prion disease cases, such as genetic CJD (gCJD) cases, exhibiting the E200K, V210I, P102L (Gerstmann\u2013Str\u00e4ussler\u2013Scheinker syndrome (GSS)), or D178N (fatal familial insomnia (FFI)) mutations in the PRNP. Interestingly, we observed enhanced levels of CSF-MDH1 in all genetic prion disease patients compared to neurological controls (without neurodegeneration). While E200K and V210I carriers showed highest levels of MDH1 with diagnostic discrimination from controls of 0.87 and 0.85 area under the curve (AUC), FFI and GSS patients exhibited only moderately higher CSF-MDH1 levels than controls. An impact of the PRNP codon 129 methionine\/valine (MV) genotype on the amount of MDH1 could be excluded. A correlation study of MDH1 levels with other neurodegenerative marker proteins revealed a significant positive correlation between CSF-MDH1 concentration with total tau (tau) but not with 14-3-3 in E200K, as well as in V210I patients. In conclusion, our study indicated the potential use of MDH1 as marker for gCJD patients which may complement the current panel of diagnostic biomarkers.<\/jats:p>","DOI":"10.3390\/biom9120800","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T10:54:10Z","timestamp":1574938450000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-2463","authenticated-orcid":false,"given":"Inga","family":"Zerr","sequence":"first","affiliation":[{"name":"Department of Neurology, National Reference Center for CJD Surveillance University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)\u2014G\u00f6ttingen campus, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Villar-Piqu\u00e9","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanda Edit","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Reference Center for CJD Surveillance University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-7767","authenticated-orcid":false,"given":"Anna","family":"Poleggi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-2486","authenticated-orcid":false,"given":"Maurizio","family":"Pocchiari","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-3324","authenticated-orcid":false,"given":"Miguel","family":"Calero","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"},{"name":"Research Program on Digital Health, Chronicity and Healthcare Services (CROSADIS-UFIEC), Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Calero","sequence":"additional","affiliation":[{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Neurology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Santana","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal"},{"name":"Neurology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3004-561 Coimbra, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-5511","authenticated-orcid":false,"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"University of Toronto, Tanz Centre for Research in Neurodegenerative Disease, Toronto, ON M5S 3H2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-7497","authenticated-orcid":false,"given":"Franc","family":"Llorens","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Reference Center for CJD Surveillance University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5502-681X","authenticated-orcid":false,"given":"Matthias","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Reference Center for CJD Surveillance University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE)\u2014G\u00f6ttingen campus, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1551","DOI":"10.1002\/humu.21281","article-title":"PRNP allelic series from 19 years of prion protein gene sequencing at the MRC prion unit","volume":"31","author":"Beck","year":"2010","journal-title":"Hum. 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Aging"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/12\/800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:18Z","timestamp":1760189898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/12\/800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,28]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["biom9120800"],"URL":"https:\/\/doi.org\/10.3390\/biom9120800","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,28]]}}}