Related Experiment Video
Updated: Jul 30, 2026
Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular
Zhen Hong1, Chen Tian1, Tessandra Stewart1
1From the Departments of Pathology (Z.H., T.S., P.A., D.S., M.B., L.S., K.B., T.K., C.P., M.S., J.Z.), Neurology (C.P.Z.), and Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Department of Neurology (Z.H.), West China Medical School, Sichuan University, Chengdu; Department of Pathology (C.T., J.Z.), Central Laboratory (J.Z.), The First Affiliated Hospital and School of Medicine, and National Health and Disease Human Brain Tissue Resource Center (J.Z.), Zhejiang University, Hangzhou; Geriatric Research, Education, and Clinical Center (C.P.Z.) and Mental Illness Research, Education, and Clinical Centre (E.R.P.), Veterans Affairs Puget Sound Health Care System, Seattle, WA; Parkinson's Disease Research, Education, and Clinical Care Center (J.F.Q.), Portland VA Medical Center; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; Department of Pathology (T.J.M.), Stanford University School of Medicine, Palo Alto, CA; and Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway.
Objective:
To develop a reliable and fast assay to quantify the α-synuclein (α-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 α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-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 α-syn-positive and aggregated α-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 α-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 α-syn-positive and aggregated α-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 α-syn-positive EVs in CSF identify patients with PD.
