Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease
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Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease. / Karayel, Ozge; Virreira Winter, Sebastian; Padmanabhan, Shalini; Kuras, Yuliya I.; Vu, Duc Tung; Tuncali, Idil; Merchant, Kalpana; Wills, Anne Marie; Scherzer, Clemens R.; Mann, Matthias.
In: Cell Reports Medicine, Vol. 3, No. 6, 100661, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease
AU - Karayel, Ozge
AU - Virreira Winter, Sebastian
AU - Padmanabhan, Shalini
AU - Kuras, Yuliya I.
AU - Vu, Duc Tung
AU - Tuncali, Idil
AU - Merchant, Kalpana
AU - Wills, Anne Marie
AU - Scherzer, Clemens R.
AU - Mann, Matthias
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - biomarker
KW - CSF
KW - DIA
KW - LRRK2
KW - mass spectrometry
KW - Parkinson's disease
KW - proteomics
U2 - 10.1016/j.xcrm.2022.100661
DO - 10.1016/j.xcrm.2022.100661
M3 - Journal article
C2 - 35732154
AN - SCOPUS:85132594235
VL - 3
JO - Cell Reports Medicine
JF - Cell Reports Medicine
SN - 2666-3791
IS - 6
M1 - 100661
ER -
ID: 312700472