[Aiming to develop biochemical biomarkers for Parkinson's disease and related disorders]

In Parkinson's disease (PD), its diagnosis, measurement of progression and response to therapeutic intervention currently rely upon clinical observation. However, there remains a critical need for validated biomarkers for PD. Among proteins in cerebrospinal fluid (CSF) there is ample biochemical, pathological, and genetic evidence that the metabolism of α-synuclein (α-syn) plays a crucial role in the pathogenesis of PD. We first reported that PD patients had significantly lower α-syn levels in their CSF than the control groups. We then investigated the levels of α-syn oligomers in CSF using a specific self-developed ELISA. The levels of α-syn oligomers were significantly higher in the PD compared to the controls, with a sensitivity of 75.0% and a specificity of 87.5% for the diagnosis of PD, demonstrating that CSF α-syn oligomers can be a useful biomarker for diagnosis of PD. We have recently developed a proteomic profiling strategy for PD. CSF proteins were purified with C8 magnetic beads, and mass spectra were obtained by mass spectrometry. By building a Support vector machine classifier, PD and multiple system atrophy (MSA) were classified effectively with good cross-validation accuracy. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of PD and MSA.