Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach

Abstract The aim of our study was to investigate cerebrospinal fluid (CSF) tryptic peptide profiles as potential diagnostic biomarkers for the discrimination of parkinsonian disorders. CSF samples were collected from individuals with parkinsonism, who had an uncertain diagnosis at the time of inclus...

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Autores principales:	Tainá M. Marques, Anouke van Rumund, Iris Kersten, Ilona B. Bruinsma, Hans J.C.T. Wessels, Jolein Gloerich, Charlotte Kaffa, Rianne A. J. Esselink, Bastiaan R. Bloem, H. Bea Kuiperij, Marcel M. Verbeek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/20d7ff2906c34b81b81ceb6c702ca96f
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spelling	oai:doaj.org-article:20d7ff2906c34b81b81ceb6c702ca96f2021-12-05T12:17:23ZIdentification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach10.1038/s41531-021-00249-92373-8057https://doaj.org/article/20d7ff2906c34b81b81ceb6c702ca96f2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00249-9https://doaj.org/toc/2373-8057Abstract The aim of our study was to investigate cerebrospinal fluid (CSF) tryptic peptide profiles as potential diagnostic biomarkers for the discrimination of parkinsonian disorders. CSF samples were collected from individuals with parkinsonism, who had an uncertain diagnosis at the time of inclusion and who were followed for up to 12 years in a longitudinal study. We performed shotgun proteomics to identify tryptic peptides in CSF of Parkinson’s disease (PD, n = 10), multiple system atrophy patients (MSA, n = 5) and non-neurological controls (n = 10). We validated tryptic peptides with differential levels between PD and MSA using a newly developed selected reaction monitoring (SRM) assay in CSF of PD (n = 46), atypical parkinsonism patients (AP; MSA, n = 17; Progressive supranuclear palsy; n = 8) and non-neurological controls (n = 39). We identified 191 tryptic peptides that differed significantly between PD and MSA, of which 34 met our criteria for SRM development. For 14/34 peptides we confirmed differences between PD and AP. These tryptic peptides discriminated PD from AP with moderate-to-high accuracy. Random forest modelling including tryptic peptides plus either clinical assessments or other CSF parameters (neurofilament light chain, phosphorylated tau protein) and age improved the discrimination of PD vs. AP. Our results show that the discovery of tryptic peptides by untargeted and subsequent validation by targeted proteomics is a suitable strategy to identify potential CSF biomarkers for PD versus AP. Furthermore, the tryptic peptides, and corresponding proteins, that we identified as differential biomarkers may increase our current knowledge about the disease-specific pathophysiological mechanisms of parkinsonism.Tainá M. MarquesAnouke van RumundIris KerstenIlona B. BruinsmaHans J.C.T. WesselsJolein GloerichCharlotte KaffaRianne A. J. EsselinkBastiaan R. BloemH. Bea KuiperijMarcel M. VerbeekNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Tainá M. Marques Anouke van Rumund Iris Kersten Ilona B. Bruinsma Hans J.C.T. Wessels Jolein Gloerich Charlotte Kaffa Rianne A. J. Esselink Bastiaan R. Bloem H. Bea Kuiperij Marcel M. Verbeek Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
description	Abstract The aim of our study was to investigate cerebrospinal fluid (CSF) tryptic peptide profiles as potential diagnostic biomarkers for the discrimination of parkinsonian disorders. CSF samples were collected from individuals with parkinsonism, who had an uncertain diagnosis at the time of inclusion and who were followed for up to 12 years in a longitudinal study. We performed shotgun proteomics to identify tryptic peptides in CSF of Parkinson’s disease (PD, n = 10), multiple system atrophy patients (MSA, n = 5) and non-neurological controls (n = 10). We validated tryptic peptides with differential levels between PD and MSA using a newly developed selected reaction monitoring (SRM) assay in CSF of PD (n = 46), atypical parkinsonism patients (AP; MSA, n = 17; Progressive supranuclear palsy; n = 8) and non-neurological controls (n = 39). We identified 191 tryptic peptides that differed significantly between PD and MSA, of which 34 met our criteria for SRM development. For 14/34 peptides we confirmed differences between PD and AP. These tryptic peptides discriminated PD from AP with moderate-to-high accuracy. Random forest modelling including tryptic peptides plus either clinical assessments or other CSF parameters (neurofilament light chain, phosphorylated tau protein) and age improved the discrimination of PD vs. AP. Our results show that the discovery of tryptic peptides by untargeted and subsequent validation by targeted proteomics is a suitable strategy to identify potential CSF biomarkers for PD versus AP. Furthermore, the tryptic peptides, and corresponding proteins, that we identified as differential biomarkers may increase our current knowledge about the disease-specific pathophysiological mechanisms of parkinsonism.
format	article
author	Tainá M. Marques Anouke van Rumund Iris Kersten Ilona B. Bruinsma Hans J.C.T. Wessels Jolein Gloerich Charlotte Kaffa Rianne A. J. Esselink Bastiaan R. Bloem H. Bea Kuiperij Marcel M. Verbeek
author_facet	Tainá M. Marques Anouke van Rumund Iris Kersten Ilona B. Bruinsma Hans J.C.T. Wessels Jolein Gloerich Charlotte Kaffa Rianne A. J. Esselink Bastiaan R. Bloem H. Bea Kuiperij Marcel M. Verbeek
author_sort	Tainá M. Marques
title	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
title_short	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
title_full	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
title_fullStr	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
title_full_unstemmed	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
title_sort	identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/20d7ff2906c34b81b81ceb6c702ca96f
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Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach

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