PXD026491

PXD026491 is an original dataset announced via ProteomeXchange.

Title	Proteome Profiling of Cerebrospinal Fluid reveals novel biomarker candidates for Parkinson’s disease
Description	Parkinson's disease (PD) is a growing burden worldwide, and despite ongoing efforts to find reliable biomarkers for early and differential diagnosis, prognosis and disease monitoring, there is no biofluid biomarker used in clinical routine to date. Cerebrospinal fluid (CSF) is collected often and should closely reflect structural and functional alterations in PD patients' brains. Here we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling to find specific biomarkers and identify disease-related changes in CSF protein levels in PD. From two independent cohorts consisting of more than 200 individuals, our workflow reproducibly quantified over 1,700 proteins from minimal sample amounts. Combined with machine learning, this identified a group of several proteins, including OMD, CD44, VGF, PRL, and MAN2B1 that were altered in PD patients or significantly correlate with clinical scores, indicative of disease progression. Interestingly, we uncovered signatures of enhanced neuroinflammation in patients with familial PD (LRRK2 G2019S carriers) as indicated by increased levels of CTSS, PLD4, HLA-DRA, HLA-DRB1, and HLA-DPA1. A comparison with urinary proteome changes in PD patients revealed a large overlap in protein composition PD-associated changes in these body fluids, including lysosomal factors like CTSS. Our results validate MS-based proteomics of CSF as a valuable strategy for biomarker discovery and patient stratification in a neurodegenerative disease like PD. Consistent proteomic signatures across two independent CSF cohorts and previously acquired urinary proteome profiles open up new avenues to improve our understanding of PD pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:27.316.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-04 08:15:56	ID requested
1	2022-06-01 11:24:51	announced
⏵ 2	2024-10-22 05:37:28	announced	2024-10-22: Updated project metadata.

Bader JM, Geyer PE, M, ü, ller JB, Strauss MT, Koch M, Leypoldt F, Koertvelyessy P, Bittner D, Schipke CG, Incesoy EI, Peters O, Deigendesch N, Simons M, Jensen MK, Zetterberg H, Mann M, Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease. Mol Syst Biol, 16(6):e9356(2020) [pubmed]

10.15252/msb.20199356;

submitter keyword: proteomics, CSF, Parkinson's disease, biomarker

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/06/PXD026491

PRIDE project URI

• PRIDE
  1. PXD026491
     1. Label: PRIDE project
     2. Name: Proteome Profiling of Cerebrospinal Fluid reveals novel biomarker candidates for Parkinson’s disease