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  Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease

Karayel, O., Winter, S., Padmanabhan, S., Kuras I, Y., Tung Vu, D., Tuncali, I., et al. (2022). Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease. Cell Reports Medicine, 3(6): 100661. doi:10.1016/j.xcrm.2022.100661.

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 Creators:
Karayel, Ozge1, Author           
Winter, Sebastian1, Author           
Padmanabhan, Shalini2, Author
Kuras I, Yuliya2, Author
Tung Vu, Duc1, Author           
Tuncali, Idil2, Author
Merchant, Kalpana2, Author
Wills, Anne-Marie2, Author
Scherzer, Clemens R.2, Author
Mann, Matthias1, Author           
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              

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Free keywords: ALPHA-SYNUCLEIN; LRRK2 KINASE; CATHEPSIN-S; HLA-DR; MUTATIONS; SULFOTRANSFERASE; EPIDEMIOLOGY; ASSOCIATION; EXPRESSION; MIGRATIONCell Biology; Research & Experimental Medicine;
 Abstract: Parkinson's disease (PD) is a growing burden worldwide, and there is no reliable biomarker used in clinical routines to date. Cerebrospinal fluid (CSF) is routinely collected in patients with neurological symptoms and should closely reflect alterations in PD patients' brains. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomics workflow for CSF proteome profiling. From two independent cohorts with over 200 individuals, our workflow reproducibly quantifies over 1,700 proteins from minimal CSF amounts. Machine learning determines OMD, CD44, VGF, PRL, and MAN2B1 to be altered in PD patients or to significantly correlate with clinical scores. We also uncover signatures of enhanced neuroinflammation in LRRK2 G2019S carriers, as indicated by increased levels of CTSS, PLD4, and HLA proteins. A comparison with our previously acquired urinary proteomes reveals a large overlap in PD-associated changes, including lysosomal proteins, opening up new avenues to improve our understanding of PD pathogenesis.

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Language(s): eng - English
 Dates: 2022
 Publication Status: Published online
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Cell Reports Medicine
Source Genre: Journal
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Publ. Info: RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS : ELSEVIER
Pages: - Volume / Issue: 3 (6) Sequence Number: 100661 Start / End Page: - Identifier: ISSN: 2666-3791