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Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease

To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligo...

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Autores principales: Parnetti, Lucilla, Chiasserini, Davide, Persichetti, Emanuele, Eusebi, Paolo, Varghese, Shiji, Qureshi, Mohammad M, Dardis, Andrea, Deganuto, Marta, De Carlo, Claudia, Castrioto, Anna, Balducci, Chiara, Paciotti, Silvia, Tambasco, Nicola, Bembi, Bruno, Bonanni, Laura, Onofrj, Marco, Rossi, Aroldo, Beccari, Tommaso, El-Agnaf, Omar, Calabresi, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282452/
https://www.ncbi.nlm.nih.gov/pubmed/24436092
http://dx.doi.org/10.1002/mds.25772
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author Parnetti, Lucilla
Chiasserini, Davide
Persichetti, Emanuele
Eusebi, Paolo
Varghese, Shiji
Qureshi, Mohammad M
Dardis, Andrea
Deganuto, Marta
De Carlo, Claudia
Castrioto, Anna
Balducci, Chiara
Paciotti, Silvia
Tambasco, Nicola
Bembi, Bruno
Bonanni, Laura
Onofrj, Marco
Rossi, Aroldo
Beccari, Tommaso
El-Agnaf, Omar
Calabresi, Paolo
author_facet Parnetti, Lucilla
Chiasserini, Davide
Persichetti, Emanuele
Eusebi, Paolo
Varghese, Shiji
Qureshi, Mohammad M
Dardis, Andrea
Deganuto, Marta
De Carlo, Claudia
Castrioto, Anna
Balducci, Chiara
Paciotti, Silvia
Tambasco, Nicola
Bembi, Bruno
Bonanni, Laura
Onofrj, Marco
Rossi, Aroldo
Beccari, Tommaso
El-Agnaf, Omar
Calabresi, Paolo
author_sort Parnetti, Lucilla
collection PubMed
description To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric α-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of β-glucocerebrosidase, β-mannosidase, β-hexosaminidase, and β-galactosidase were measured with established enzymatic assays, while α-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the β-glucocerebrosidase-encoding gene (GBA1). In the PD group, β-glucocerebrosidase activity was reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity (P < 0.05); conversely, β-hexosaminidase activity was significantly increased (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total α-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of α-synuclein oligomers, with a higher oligomeric/total α-synuclein ratio in PD patients when compared with controls (P < 0.001). A combination of β-glucocerebrosidase activity, oligomeric/total α-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD.
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spelling pubmed-42824522015-01-15 Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease Parnetti, Lucilla Chiasserini, Davide Persichetti, Emanuele Eusebi, Paolo Varghese, Shiji Qureshi, Mohammad M Dardis, Andrea Deganuto, Marta De Carlo, Claudia Castrioto, Anna Balducci, Chiara Paciotti, Silvia Tambasco, Nicola Bembi, Bruno Bonanni, Laura Onofrj, Marco Rossi, Aroldo Beccari, Tommaso El-Agnaf, Omar Calabresi, Paolo Mov Disord Research Articles To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of β-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric α-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of β-glucocerebrosidase, β-mannosidase, β-hexosaminidase, and β-galactosidase were measured with established enzymatic assays, while α-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n = 44) was also screened for mutations in the β-glucocerebrosidase-encoding gene (GBA1). In the PD group, β-glucocerebrosidase activity was reduced (P < 0.05) and patients at earlier stages showed lower enzymatic activity (P < 0.05); conversely, β-hexosaminidase activity was significantly increased (P < 0.05). Eight PD patients (18%) presented GBA1 sequence variations; 3 of them were heterozygous for the N370S mutation. Levels of total α-synuclein were significantly reduced (P < 0.05) in PD, in contrast to increased levels of α-synuclein oligomers, with a higher oligomeric/total α-synuclein ratio in PD patients when compared with controls (P < 0.001). A combination of β-glucocerebrosidase activity, oligomeric/total α-synuclein ratio, and age gave the best performance in discriminating PD from neurological controls (sensitivity 82%; specificity 71%, area under the receiver operating characteristic curve = 0.87). These results demonstrate the possibility of detecting lysosomal dysfunction in CSF and further support the need to combine different biomarkers for improving the diagnostic accuracy of PD. BlackWell Publishing Ltd 2014-07 2014-01-16 /pmc/articles/PMC4282452/ /pubmed/24436092 http://dx.doi.org/10.1002/mds.25772 Text en © 2014 The Authors. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Parnetti, Lucilla
Chiasserini, Davide
Persichetti, Emanuele
Eusebi, Paolo
Varghese, Shiji
Qureshi, Mohammad M
Dardis, Andrea
Deganuto, Marta
De Carlo, Claudia
Castrioto, Anna
Balducci, Chiara
Paciotti, Silvia
Tambasco, Nicola
Bembi, Bruno
Bonanni, Laura
Onofrj, Marco
Rossi, Aroldo
Beccari, Tommaso
El-Agnaf, Omar
Calabresi, Paolo
Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title_full Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title_fullStr Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title_full_unstemmed Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title_short Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson's Disease
title_sort cerebrospinal fluid lysosomal enzymes and alpha-synuclein in parkinson's disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282452/
https://www.ncbi.nlm.nih.gov/pubmed/24436092
http://dx.doi.org/10.1002/mds.25772
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