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Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients
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–Jakob disease (sCJD) patients revealed a highly significant u...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995564/ https://www.ncbi.nlm.nih.gov/pubmed/31795176 http://dx.doi.org/10.3390/biom9120800 |
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author | 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 |
author_facet | 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 |
author_sort | Zerr, Inga |
collection | PubMed |
description | 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–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–Sträussler–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. |
format | Online Article Text |
id | pubmed-6995564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69955642020-02-13 Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients 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 Biomolecules Article 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–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–Sträussler–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. MDPI 2019-11-28 /pmc/articles/PMC6995564/ /pubmed/31795176 http://dx.doi.org/10.3390/biom9120800 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title | Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title_full | Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title_fullStr | Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title_full_unstemmed | Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title_short | Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients |
title_sort | evaluation of human cerebrospinal fluid malate dehydrogenase 1 as a marker in genetic prion disease patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995564/ https://www.ncbi.nlm.nih.gov/pubmed/31795176 http://dx.doi.org/10.3390/biom9120800 |
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