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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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