PXD028888-1

PXD028888 is an original dataset announced via ProteomeXchange.

Title	Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach
Description	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 discovery of tryptic peptides by untargeted and subsequent validation by targeted proteomics is a suitable strategy to identify novel 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.
HostingRepository	PanoramaPublic
AnnounceDate	2022-01-10
AnnouncementXML	Submission_2022-01-10_07:50:21.266.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tainá Macherini Marques
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Xevo TQ-S

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-01 10:10:43	ID requested
⏵ 1	2022-01-10 07:50:22	announced

Marques TM, van Rumund A, Kersten I, Bruinsma IB, Wessels HJCT, Gloerich J, Kaffa C, Esselink RAJ, Bloem BR, Kuiperij HB, Verbeek MM, Identification of cerebrospinal fluid biomarkers for parkinsonism using a proteomics approach. NPJ Parkinsons Dis, 7(1):107(2021) [pubmed]

submitter keyword: Parkinson’s disease, multiple system atrophy, cerebrospinal fluid, biomarkers, mass spectrometry, selected reaction monitoring

Marcel Verbeek
contact affiliation	Radboud University Medical Center
contact email	Marcel.Verbeek@radboudumc.nl
lab head
Tainá Macherini Marques
contact affiliation	Radboud University Medical Center
contact email	taina.marques@uni.lu
dataset submitter

Panorama Public dataset URI