Though underlying mechanisms remain to be defined, alterations in plasma total and nervous system derived exosomal (NDE) α-synuclein concentrations are likely associated with Parkinson disease (PD) progression, especially in the aspect of cognitive impairment during the early stages of the disease. This according to a recent study that explored the utility of plasma α-synuclein in the prodromal phase of PD. Plasma total and NDE α-synuclein were evaluated in baseline and in 2-year follow-up samples from 256 individuals recruited as part of the Parkinson's Associated Risk Syndrome (PARS) study. Researchers found:

• Baseline and longitudinal increases in total α-synuclein predicted progression of cognitive decline in hyposmic individuals with dopamine transporter (DAT) binding reduction.
• On the other hand, a longitudinal decrease in NDE α-synuclein predicted worsening cognitive scores in hyposmic individuals with DAT binding reduction.
• Finally, in individuals with faster DAT progression, decreasing NDE/total α-synuclein ratio was associated with a larger reduction in DAT from baseline to follow-up.