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Microvesicles: Biomarker and Vehicle for the Propagation of Pathological Forms of Alpha-synuclein

Study Rationale:
All living cells release extracellular vesicles composed of membrane proteins and lipids as well as components of the cell. These vesicles are important in cell-to-cell communication. In Parkinson’s disease (PD), pathological forms of the protein alpha-synuclein have been reported in certain populations of peripheral blood cells. Here, we plan to investigate whether extracellular vesicles, which derive from peripheral blood cells, can serve as disease-specific markers and/or be implicated in disease progression.

We hypothesize that circulating extracellular vesicles in plasma 1) can serve as a biomarker in PD as well as 2) contribute to the disease process by transporting forms of pathological alpha-synuclein from peripheral circulation to the central nervous system.

Study Design:
We will perform a quantitative analysis of the subpopulations of extracellular vesicles present in the bloodstream. This will highlight differences in the number and nature of extracellular vesicles between PD patients and controls and potentially lead to the identification of novel biomarkers. The protein content of extracellular vesicles will also be studied, unraveling the potential role of extracellular vesicles to the pathophysiology.

Impact on Diagnosis/Treatment of Parkinson’s Disease: 
The demonstration of differences in extracellular vesicles has the potential to reveal novel biomarkers and unravel new disease mechanisms for PD.

Next Steps for Development:
If we observe a significant difference in extracellular vesicle populations in PD patients, studies on larger cohorts will be undertaken to investigate how these changes correlate with disease progression and subtypes. If pathological forms of alpha-synuclein are detected within extracellular vesicles, pre-clinical models will be used to determine how extracellular vesicles can migrate to the brain and participate in disease progression. 


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