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

Abstract

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 a-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 a-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.