Validation of CSF Alpha-synuclein as a Biomarker for Parkinson's disease

Objective/Rationale:
Accumulation of alpha-synuclein within certain nerve cells represents one of the hallmarks of classical Parkinson disease. Our team recently discovered that alpha-synuclein levels in cerebrospinal fluid (CSF) are significantly lower in PD patients than in age-matched controls. As a next step of our biomarker study (second phase), we will examine whether a low concentration of CSF alpha-synuclein can distinguish subjects with typical PD from those patients that suffer from other neurological conditions.
Project Description:
We will validate our recent findings in an independent cohort of over 450 subjects diagnosed with various neurodegenerative conditions. The study participants will include foremost patients with typical PD, atypical parkinsonism, Alzheimer disease and Lewy body dementia. There, CSF and blood alpha-synuclein concentrations will be measured by an existing ELISA protocol and will be compared with other CSF- and blood-based, routine laboratory markers. To facilitate the third phase of our biomarker study, which will see the use of our test at other centers for additional cohorts, we will also optimize our current ELISA protocol; its current sensitivity will be enhanced through an upgrade from our colorimetric- to a fluorescence-based assay system. Here, we will validate this optimized ELISA protocol by retesting the specimens collected above.
Relevance to Diagnosis and Treatment of Parkinson Disease:
The goal of our study is to add a laboratory marker to the clinical evaluation of subjects with parkinsonism. 
Anticipated Outcome:
We expect to learn two things: (1) whether two new laboratory values, i.e., the measurement of alpha-synuclein concentration in blood and in CSF from living donors, can help differentiate between classical PD and other conditions; and (2) whether improving the sensitivity of our current ELISA protocol will result in an equally reliable and standardized laboratory assay, which allows for the accurate quantification of alpha-synuclein in human fluids by other investigators.