Abstract

OBJECTIVE: To develop a reliable and fast assay to quantify the alpha-synuclein (alpha-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).METHODS: A cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying alpha-syn or aggregated alpha-syn were quantified using antibodies against total or aggregated alpha-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.RESULTS: No significant differences in the number and size distribution of total EVs between patients with PD and HCs in CSF were observed. When examining the total alpha-syn-positive and aggregated alpha-syn-positive EV subpopulations, the proportions of both among all detected CSF EVs were significantly lower in patients with PD compared to HCs (p < 0.0001). While each EV subpopulation showed better diagnostic sensitivity and specificity than total CSF alpha-syn measured directly with an immunoassay, a combination of the 2 EV subpopulations demonstrated a diagnostic accuracy that attained clinical relevance (area under curve 0.819, sensitivity 80%, specificity 71%).CONCLUSION: Using newly established, sensitive nanoscale flow cytometry assays, we have demonstrated that total alpha-syn-positive and aggregated alpha-syn-positive EVs in CSF may serve as a helpful tool in PD diagnosis.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that total and aggregated alpha-syn-positive EVs in CSF identify patients with PD.

View details for DOI 10.1212/WNL.0000000000011853

View details for PubMedID 34032594