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