Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients
| Autor: | Zerr, Inga, Villar-Piqué, Anna, Schmitz, Vanda Edit, Poleggi, Anna, Pocchiari, Maurizio, Sánchez-Valle, Raquel, Calero, Miguel, Calero, Olga, Baldeiras, Inês, Santana, Isabel, Kovacs, Gabor G., Llorens, Franc, Schmitz, Matthias |
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| Přispěvatelé: | Instituto de Salud Carlos III, Instituto de Salud Carlos III - ISCIII |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male diagnostic biomarker tau Proteins PRNP codon 129 MV genotypes Article cerebrospinal fluid Prion Diseases Malate Dehydrogenase ddc:570 cerebrospinal fluid [Malate Dehydrogenase] Humans Aged Malalties neurodegeneratives Líquid cefalorraquidi Neurodegenerative Diseases Middle Aged Up-Regulation cerebrospinal fluid [14-3-3 Proteins] Cerebrospinal fluid cerebrospinal fluid [Biomarkers] cerebrospinal fluid [tau Proteins] 14-3-3 Proteins Female mitochondrial malate dehydrogenase 1 cerebrospinal fluid [Prion Diseases] genetic prion diseases Biomarkers |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Biomolecules Repisalud Instituto de Salud Carlos III (ISCIII) Biomolecules 9(12), 800 (2019). doi:10.3390/biom9120800 Volume 9 Issue 12 |
| DOI: | 10.3390/biom9120800 |
| Popis: | 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&ndash Jakob 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&ndash Strä ussler&ndash Scheinker 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. |
| Databáze: | OpenAIRE |
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