Abstract

Biomarkers for Parkinson’s Disease: What has Been Achieved and What Needs to Come

Brit Mollenhauer, Head of Clinical Research, Paracelsus-Elena-Klinik

Many fundamental decisions in clinical routine are based on biomarkers, but no widely applicable marker is available for Parkinson’s disease (PD) with three major problems: (1) our clinical diagnosis is too late, when more than 50% of dopaminergic neurons are already degenerated; (2) the diagnosis PD is wrong in 10-20% even when diagnosed by movement disorder experts and (3) upcoming neuropreventive treatments may fail, due to the lack of an objective progression marker. The presence of total alpha-synuclein in cerebrospinal fluid (CSF) has long been debated, but has been proven in 2008 by mass spectrometry (Mollenhauer et al., 2008). Several assays for the quantification of total alpha-synuclein in CSF showed a decrease in alpha-synuclein-related disorders: PD, Dementia with Lewy Bodies  and Multiple System Atrophy (Tokuda et al., 2006; Mollenhauer et al., 2011; Hong et al., 2010). We have shown that CSF alpha-synuclein is derived from neurons of the central nervous system (Mollenhauer et al., 2012). The decrease could recently also been found in drug-naïve PD cases versus healthy controls in our single center study (“DeNoPa”)(Mollenhauer et al., 2013) and our multicenter study (“PPMI”) (Kang et al., 2013). We established The DeNoPa cohort on 159 at enrolment drug-naïve PD subjects and 110 healthy controls. CSF, blood, urine, saliva, nasal fluid and stool samples will be used to explore new biomarkers by cross-omics and further validation. In parallel we established a new multiplex on an electrochemiluminescence platform (Mesoscale Discovery) to quantify total alpha-synuclein, total tau protein, ß-amyloid (1-42) and DJ-1 with a single measurement in a single CSF sample of 50 ul.