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Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease
There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD diagnosis. Preliminary evidences sh...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978246/ https://www.ncbi.nlm.nih.gov/pubmed/24744728 http://dx.doi.org/10.3389/fnagi.2014.00053 |
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author | Parnetti, Lucilla Farotti, Lucia Eusebi, Paolo Chiasserini, Davide De Carlo, Claudia Giannandrea, David Salvadori, Nicola Lisetti, Viviana Tambasco, Nicola Rossi, Aroldo Majbour, Nour K. El-Agnaf, Omar Calabresi, Paolo |
author_facet | Parnetti, Lucilla Farotti, Lucia Eusebi, Paolo Chiasserini, Davide De Carlo, Claudia Giannandrea, David Salvadori, Nicola Lisetti, Viviana Tambasco, Nicola Rossi, Aroldo Majbour, Nour K. El-Agnaf, Omar Calabresi, Paolo |
author_sort | Parnetti, Lucilla |
collection | PubMed |
description | There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD diagnosis. Preliminary evidences show that the combination of CSF t-α-syn and classical Alzheimer's disease (AD) biomarkers—β-amyloid 1–42 (Aβ(42)), total tau (t-tau), phosphorylated tau (p-tau)—differentiate PD patients from controls, and that reduced levels of Aβ(42) represent a predictive factor for development of cognitive deterioration in PD. In this prospective study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein species—t-α-syn and o-α-syn—and classical AD biomarkers may help in differentiating PD from neurological controls, and if these biomarkers may predict cognitive decline. The median of follow-up duration was 3 years (range: 2–6 years). Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used for monitoring cognitive changes along time, being administered once a year. Oligo/total α-syn ratio (o/t-α-syn ratio) confirmed its diagnostic value, significantly contributing to the discrimination of PD from neurological controls. A greater diagnostic accuracy was reached when combining o/t-α-syn and Aβ(42)/tau ratios (Sens = 0.70, Spec = 0.84, AUC = 0.82; PPV = 0.89, NPV = 0.62, LR+ = 4.40, DOR = 12.52). Low CSF Aβ(42) level was associated with a higher rate of MMSE and MoCA decline, confirming its role as independent predictive factor for cognitive decline in PD. None of the other biomarkers assessed (t-tau, p-tau, t-α-syn and o-α-syn) showed to have prognostic value. We conclude that combination of CSF o/t-α-syn and Aβ(42)/tau ratios improve the diagnostic accuracy of PD. PD patients showing low CSF Aβ(42) levels at baseline are more prone to develop cognitive decline. |
format | Online Article Text |
id | pubmed-3978246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-39782462014-04-17 Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease Parnetti, Lucilla Farotti, Lucia Eusebi, Paolo Chiasserini, Davide De Carlo, Claudia Giannandrea, David Salvadori, Nicola Lisetti, Viviana Tambasco, Nicola Rossi, Aroldo Majbour, Nour K. El-Agnaf, Omar Calabresi, Paolo Front Aging Neurosci Neuroscience There is a great interest in developing cerebrospinal fluid (CSF) biomarkers for diagnosis and prognosis of Parkinson's disease (PD). CSF alpha synuclein (α-syn) species, namely total and oligomeric α-syn (t-α-syn and o-α-syn), have shown to be of help for PD diagnosis. Preliminary evidences show that the combination of CSF t-α-syn and classical Alzheimer's disease (AD) biomarkers—β-amyloid 1–42 (Aβ(42)), total tau (t-tau), phosphorylated tau (p-tau)—differentiate PD patients from controls, and that reduced levels of Aβ(42) represent a predictive factor for development of cognitive deterioration in PD. In this prospective study carried out in 44 PD patients and 25 neurological controls we wanted to verify whether the combination of CSF α-synuclein species—t-α-syn and o-α-syn—and classical AD biomarkers may help in differentiating PD from neurological controls, and if these biomarkers may predict cognitive decline. The median of follow-up duration was 3 years (range: 2–6 years). Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used for monitoring cognitive changes along time, being administered once a year. Oligo/total α-syn ratio (o/t-α-syn ratio) confirmed its diagnostic value, significantly contributing to the discrimination of PD from neurological controls. A greater diagnostic accuracy was reached when combining o/t-α-syn and Aβ(42)/tau ratios (Sens = 0.70, Spec = 0.84, AUC = 0.82; PPV = 0.89, NPV = 0.62, LR+ = 4.40, DOR = 12.52). Low CSF Aβ(42) level was associated with a higher rate of MMSE and MoCA decline, confirming its role as independent predictive factor for cognitive decline in PD. None of the other biomarkers assessed (t-tau, p-tau, t-α-syn and o-α-syn) showed to have prognostic value. We conclude that combination of CSF o/t-α-syn and Aβ(42)/tau ratios improve the diagnostic accuracy of PD. PD patients showing low CSF Aβ(42) levels at baseline are more prone to develop cognitive decline. Frontiers Media S.A. 2014-03-31 /pmc/articles/PMC3978246/ /pubmed/24744728 http://dx.doi.org/10.3389/fnagi.2014.00053 Text en Copyright © 2014 Parnetti, Farotti, Eusebi, Chiasserini, De Carlo, Giannandrea, Salvadori, Lisetti, Tambasco, Rossi, Majbour, El-Agnaf, and Calabresi. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Parnetti, Lucilla Farotti, Lucia Eusebi, Paolo Chiasserini, Davide De Carlo, Claudia Giannandrea, David Salvadori, Nicola Lisetti, Viviana Tambasco, Nicola Rossi, Aroldo Majbour, Nour K. El-Agnaf, Omar Calabresi, Paolo Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title | Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title_full | Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title_fullStr | Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title_full_unstemmed | Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title_short | Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease |
title_sort | differential role of csf alpha-synuclein species, tau, and aβ42 in parkinson's disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978246/ https://www.ncbi.nlm.nih.gov/pubmed/24744728 http://dx.doi.org/10.3389/fnagi.2014.00053 |
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