Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

Abstract

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, Aβ42, S100β, 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, S100β 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 Aβ42 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.

CLU rs11136000 Promotes Early Cognitive Decline in Parkinson's Disease

“…As expected, PD patients showed motor and cognitive compromise with respect to controls and also had alterations in common biomarkers of neural damage . High‐risk CLU patients showed both a quantitative (lower MoCA scores) and qualitative (higher prevalence of clinically diagnosed PD‐MCI or PDD) cognitive decline at follow‐up.…”

Targeted Multiple Reaction Monitoring Analysis of CSF Identifies UCHL1 and GPNMB as Candidate Biomarkers for ALS

“…UCHL1 has also been shown to destabilize mTOR complex 1 by antagonizing the ubiquitination of raptor (Yang et al 2015a). Analysis of UCHL1 in CSF supports the idea that this protein may have diagnostic value in multivariate models of PD but needs further validation in additional cohorts (Dos Santos et al 2018).…”

DJ-1 in Parkinson’s Disease: Clinical Insights and Therapeutic Perspectives

“…The detection of biomarkers able to identify PD pathology in the early phases of the disease is a priority for the scientific community. In this regard, DJ-1 has been found to be constitutively present in the cerebrospinal fluid (CSF), and several groups have analyzed its potential as a biomarker for PD, with unclear and conflicting results (for a review see [62,63]). Notably, CSF DJ-1 levels were found to be significantly increased as a function of age, especially in controls, while the age dependence became weaker in patients with PD [64].…”