Early Diagnosis of Parkinson's Disease: A New Biomarker

Identifying people with Parkinson's disease (PD) in its prodromal phase has become a priority to open a window for disease-modifying therapies.

The investigators aimed to evaluate a blood α-synuclein seed amplification assay (α-syn SAA) as a new biomarker to diagnose PD in the prodromal phase.

In the TREND study (University of Tübingen), biennial blood samples were taken from 1201 individuals with/without increased risk of PD for 4 to 10 years. We retrospectively analyzed blood samples from 12 participants diagnosed with PD during the study to detect and amplify pathological conformers of α-synuclein derived from neuronal extracellular vesicles using (1) immunoblot analysis with an antibody against these conformers and (2) an α-syn SAA. In addition, blood samples from 13 healthy individuals from the TREND cohort and from 20 individuals with isolated REM sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed.

All individuals with PD showed positive immunoblots and a positive α-syn SAA at diagnosis. In addition, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA.

Conclusions

They demonstrate the ability to detect and amplify pathological conformers of α-synuclein in peripheral blood up to 10 years before clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD.