Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein–Containing Extracellular Vesicles
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
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.
Glossary
- α-syn=
- α-synuclein;
- AUC=
- area under the curve;
- CI=
- confidence interval;
- CV=
- coefficient of variation;
- DLB=
- dementia with Lewy bodies;
- EV=
- extracellular vesicle;
- H&Y=
- Hoehn & Yahr;
- HC=
- healthy control;
- IgG=
- immunoglobulin G;
- LEDD=
- levodopa equivalent daily dose;
- MD=
- difference in means;
- MoCA=
- Montreal Cognitive Assessment;
- NTA=
- Nanoparticle Tracking Analysis;
- PBS=
- phosphate-buffered saline;
- PD=
- Parkinson disease;
- PFA=
- paraformaldehyde;
- PMCA=
- protein-misfolding cyclic amplification;
- ROC=
- receiver operating characteristic;
- RT-QuIC=
- real-time quaking-induced conversion;
- UPDRS=
- Unified Parkinson’s Disease Rating Scale;
- UW=
- University of Washington;
- VA=
- Veterans Affairs
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Class of Evidence: NPub.org/coe
- Received November 6, 2019.
- Accepted in final form February 5, 2021.
- © 2021 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Related Articles
- No related articles found.