000K utf8 1100 $c2018 1500 eng 2050 urn:nbn:de:gbv:8-publ-24428 2051 10.1371/journal.pone.0206536 3000 T. dos Santos, Marcia Cristina 3010 Bell, Rosie 3010 Berg, Daniela Dagmar Denise 3010 Berteau, Caroline 3010 Bujac, Sarah R. 3010 Colman, Peter 3010 Lachmann, Ingolf 3010 Mätzler, Walter 3010 Mesa, Irene R. 3010 Nogueira da Costa, Andre 3010 Perez, Luis Tosar 3010 Scheller, Dieter 3010 Schulte, Claudia 4000 Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis [T. dos Santos, Marcia Cristina] 4209 Cerebrospinal fluid (CSF) has often been used as the source of choice for biomarker discovery with the goal to support the diagnosis of neurodegenerative diseases. For this study, we selected 15 CSF protein markers which were identified in previously published clinical investigations and proposed as potential biomarkers for PD diagnosis. We aimed at investigating and confirming their suitability for early stage diagnosis of the disease. The current study was performed in a two-fold confirmatory approach. Firstly, the CSF protein markers were analysed in confirmatory cohort I comprising 80 controls and 80 early clinical PD patients. Through univariate analysis we found significant changes of six potential biomarkers ($α$-syn, DJ-1, A$β$42, S100$β$, p-Tau and t-Tau). In order to increase robustness of the observations for potential patient differentiation, we developed-based on a machine learning approach-an algorithm which enabled identifying a panel of markers which would improve clinical diagnosis. Based on that model, a panel comprised of $α$-syn, S100$β$ and UCHL1 were suggested as promising candidates. Secondly, we aimed at replicating our observations in an independent cohort (confirmatory cohort II) comprising 30 controls and 30 PD patients. The univariate analysis demonstrated A$β$42 as the only reproducible potential biomarker. Taking into account both technical and clinical aspects, these observations suggest that the large majority of the investigated CSF proteins currently proposed as potential biomarkers lack robustness and reproducibility in supporting diagnosis in the early clinical stages of PD. 4950 https://doi.org/10.1371/journal.pone.0206536$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8-publ-24428$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/publ_mods_00002442 5051 610 5550 biomarkers 5550 cerebrospinal fluid proteins 5550 CSF 5550 Parkinson's disease 5550 protein markers