TY - JOUR
T1 - Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles
AU - Hong, Zhen
AU - Tian, Chen
AU - Stewart, Tessandra
AU - Aro, Patrick
AU - Soltys, David
AU - Bercow, Matt
AU - Sheng, Lifu
AU - Borden, Kayla
AU - Khrisat, Tarek
AU - Pan, Catherine
AU - Zabetian, Cyrus P.
AU - Peskind, Elaine R.
AU - Quinn, Joseph F.
AU - Montine, Thomas J.
AU - Aasly, Jan
AU - Shi, Min
AU - Zhang, Jing
N1 - Publisher Copyright:
© 2021 American Academy of Neurology.
PY - 2021/5/4
Y1 - 2021/5/4
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000011853
DO - 10.1212/WNL.0000000000011853
M3 - Article
C2 - 34032594
AN - SCOPUS:85106888913
SN - 0028-3878
VL - 96
SP - E2332-E2345
JO - Neurology
JF - Neurology
IS - 18
ER -