Extracellular vesicles – upcoming biomarkers in Parkinson's disease's biofluids

Abstract

The search of a biomarker for an early detection of neurodegenerative diseases is one of the biggest challenges of our times. The second most common neurodegenerative disorder Parkinson's disease (PD) is characterized by misfolded alpha-synuclein (a-syn) aggregates within the central nervous system (CNS). Currently, definitive PD diagnosis still requires post-mortem brain examination. As a result, the misdiagnosis of PD based only on clinical symptoms and delayed diagnosis in advanced stages cannot be excluded. Since a-syn aggregates abnormally, it might be an interesting candidate for a biomarker for PD. Lately, extracellular vesicles (EVs) have emerged as potential biomarker in biofluids since accumulating evidence suggests that their content reflects the pathophysiological alterations occurring in their host cells. Interestingly, EVs can cross the blood-brain barrier (BBB) and thus carry information from the CNS to the periphery and vice versa. EVs seem to play a role in other neurodegenerative disorders such as Alzheimer's and prion disease, where they have also shown certain diagnostic potential. For instance, EV isolation protocols have been described to isolate brain-derived EVs from blood samples, increasing their biomarker potential in neurodegenerative disorders. The results published for PD to date are promising: pathology-associated a-syn forms are found in blood-derived EVs, although the underlying mechanisms of formation and release of a-syn-loaded EVs remain unknown. Interestingly, a-syn level correlate with the disease stage, which underlines the importance of neuronal EVs in disease monitoring. Further research extends to other biofluids, like urine, saliva, and cerebrospinal fluid, where EVs can also be found, opening multiple opportunities for more reliable PD diagnosis.