BackgroundDespite decades of intensive research, to date, there is no accepted diagnosis for Parkinson’s disease (PD) based on biochemical analysis of blood or CSF. However, neurodegeneration in the brains of PD patients begins several years before the manifestation of the clinical symptoms, pointing to serious flaw/limitations in this approach.ResultsTo explore the potential use of alpha-synuclein (α-syn) species as candidate biomarkers for PD, we generated specific antibodies directed against wide array of α-syn species, namely total-, oligomeric- and phosphorylated-Ser129-α-syn (t-, o- and p-S129-α-syn). Next we sought to employ our antibodies to develop highly specific ELISA assays to quantify α-syn species in biological samples. Finally we verified the usefulness of our assays in CSF samples from 46 PD patients and 48 age-matched healthy controls. We also assessed the discriminating power of combining multiple CSF α-syn species with classical Alzheimer’s disease biomarkers. The combination of CSF o-/t-α-syn, p-S129-α-syn and p-tau provided the best fitting predictive model for discriminating PD patients from controls. Moreover, CSF o-α-syn levels correlated significantly with the severity of PD motor symptoms (r = -0.37).ConclusionOur new ELISA assays can serve as research tools to address the unmet need for reliable CSF biomarkers for PD and related disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0072-9) contains supplementary material, which is available to authorized users.

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DJ-1 is a ubiquitous protein regulating cellular viability. Recessive mutations in the PARK7/DJ-1 gene are linked to Parkinson's disease (PD). Although the most dramatic L166P point mutation practically eliminates DJ-1 protein and function, the effects of other PD-linked mutations are subtler. Here, we investigated two recently described PD-associated DJ-1 point mutations, the A179T substitution and the P158D in-frame deletion.[A179T]DJ-1 protein was as stable as wildtype [wt]DJ-1, but the P158D mutant protein was less stable. In accord with the notion that dimer formation is essential for DJ-1 protein stability, [P158D]DJ-1 was impaired in dimer formation. Similar to our previous findings for [M26I]DJ-1, [P158D]DJ-1 bound aberrantly to apoptosis signal-regulating kinase 1. Thus, the PD-associated P158D mutation destabilizes DJ-1 protein and function. As there is also evidence for an involvement of DJ-1 in multiple system atrophy, a PDrelated a-synucleinopathy characterized by oligodendroglial cytoplasmic inclusions, we studied an oligodendroglial cell line stably expressing a-synuclein. a-Synuclein aggregate dependent microtubule retraction upon co-transfection with tubulin polymerization-promoting protein p25a was ameliorated by [wt]DJ-1. In contrast, DJ-1 mutants including P158D failed to protect in this system, where we found evidence of apoptosis signal-regulating kinase 1 (ASK1) involvement. In conclusion, the P158D point mutation may contribute to neurodegeneration by protein destabilization and hence loss of DJ-1 function.