Parkinson’s disease (PD) is characterized by aggregation of the intracellular alpha-synuclein protein and subsequent neurodegeneration. Recent findings suggest that extracellular alpha-synuclein forms could be an important mediator of alpha-synuclein toxicity and spread of alpha-synuclein pathology throughout the brain. Extracellular propagation can either exist as free protein or be encapsulated within vesicles. We will investigate whether vesicular alpha-synuclein may serve as a diagnostic biomarker in Parkinson’s disease.
Project Description:
To this end we will isolate vesicular alpha-synuclein from blood and cerebrospinal fluid of PD patients, neurologically healthy controls and patients with other neurodegenerative diseases. We will measure vesicular alpha-synuclein and determine whether this protein’s levels are increased in PD patients and patients with other diseases characterized by alpha-synuclein aggregation (e.g. Lewy Body Disease). Since small aggregates of alpha-synuclein, so-called oligomers, are assumed to be highly toxic, we will also quantify whether vesicular alpha-synuclein oligomers are increased in PD patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
A specific increase in vesicular alpha-synuclein in blood or cerebrospinal fluid (CSF) from PD patients may help to distinguish Parkinson’s patients from those with other neurodegenerative diseases. It might also shed light on pathogenic processes which underlie the disease progression.
Anticipated Outcome:
Based on our preliminary results, we expect that vesicular alpha-synuclein will be increased in CSF from PD patients and distinguish PD from other neurodegenerative diseases.