Investigating the biomarker potential and pathological role of extracellular vesicles in Parkinson’s disease.

Accumulating evidence indicates that extracellular vesicles (EVs) represent a highly interesting biomarker source, both as a total population and after enriching for specific subpopulations. Indeed, neuronal- derived EVs (nEVs) separated from peripheral sources provide a snapshot of ongoing pathological changes in the brain whereas bacterial EVs (bEVs) have shown to reflect microbial dysbiosis. Interestingly, both neuronal changes and microbial dysbiosis are evident in Parkinson’s disease (PD) patients. Additionally, EVs are believed to play a role in PD pathogenesis, as it has been shown that (n)EVs can act as transport vehicles for disease-associated proteins and bEVs can elicit immunomodulatory effects. Here, both the biomarker potential and the pathological role of (n/b)EVs will be investigated. To explore the biomarker potential, I will analyze the size and protein content of (n/b)EVs separated from plasma, nasal fluid and saliva of PD patients and healthy controls. The biofluids were chosen based on their accessibility, which is of major importance from a biomarker perspective. Additionally, to unravel the role of these (n/b)EVs in PD pathogenesis, I will identify their recipient cells and validate whether the (n/b)EVs can accelerate and/or initiate PD-like pathology in in vitro and in vivo models.