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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.

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Information & Authors

Information

Published In

Neurology®
Volume 96Number 18May 4, 2021
Pages: e2332-e2345
PubMed: 34032594

Publication History

Received: November 6, 2019
Accepted: February 5, 2021
Published online: March 23, 2021
Published in print: May 4, 2021

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Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

This study was supported by the NIH (U01 NS091272, R01 AG056711, and R21 NS104511 to J.Z. and M.S., R21/R33 MH118160 to J.Z. and T.S., R01 AG061383 and RF1 AG068406 to M.S., and P50 NS062684 to T.J.M. and C.P.Z.) and with resources and the use of facilities at the Veterans Affairs Puget Sound and Veterans Affairs Portland Health Care Systems. The content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors. The sponsors of this study had no role in the study design, data collection, analysis and interpretation, or the writing of the report. The authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Authors

Affiliations & Disclosures

Zhen Hong, MD, PhD*
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Chen Tian, MD*
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tessandra Stewart, PhD
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Department of Defense W81XWH2010784 PI, 2020-2023 NIMH MH118160, PI, 2020-2023
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Patrick Aro, MS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David Soltys, BS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Matt Bercow, BS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Lifu Sheng, PhD
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kayla Borden, BS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tarek Khrisat, BS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Catherine Pan, DDS
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Cyrus P. Zabetian, MD, MS https://orcid.org/0000-0002-7739-4306
From 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.
Disclosure
Scientific Advisory Boards:
1.
1) Scientific Advisory Council, Lewy Body Dementia Association (non-profit)
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1) Department of Veterans Affairs, I01CX001702, PI, Zabetian, 2018-2021 2) Department of Veterans Affairs, I21RX002553, PI, Zabetian, 2017-2020 3) NIH/NINDS, P50 NS062684, Leader (Analytical Core), 2015-2020 4) NIH/NINDS, P50 NS062684, Site Leader (Clinical Core), 2015-2020 5) NIH/NINDS, U01 NS100610, Co-investigator, 2016-2021 6) NIH/NINDS, U01 NS082137, Co-investigator, 2012-2017
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1) American Parkinson Disease Association, Research Grant, PI, 2007-2021
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Elaine R. Peskind, MD
From 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.
Disclosure
Scientific Advisory Boards:
1.
1) Commercial Entity: Avanir Eli Lilly Takeda Merck Acadia
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
1) Commercial entity: Acadia
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
1) Commercial entiry: Eli Lilly
Research Support, Government Entities:
1.
VA R&D, I01RX000521, PI, 3/1/11-2/28/19 VA R&D, I01RX001195, PI, 8/1/13-7/31/17 VA R&D, I01CX001049, PI, 1/1/14-12/31/17 NIH, P50AG005136, Clinical Core Director, 5/1/00-4/30/17
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
1) Commercial entity: Bristol Myers Squibb
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Joseph F. Quinn, MD
From 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.
Disclosure
Scientific Advisory Boards:
1.
vTv Pharmaceuticals, Retrophin pharmaceuticals, Alzheimer's Disease Cooperative Study
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Site PI for multi-center clinical trials: Sanofi, Ascend, Neuraly
Research Support, Government Entities:
1.
VA Merit Review Grant IO1BX003440, PI, 4/1/18-3/30/22 NIH-R01 AG059392, co-I, 2/15/19-11/30/24 NIH-U19 AT010829, co-I, 07/01/2020 06/30/2025 NIH R01AG057611, co-I, 8/15/17-4/30/22 NIH-P30AG066518, co-I, 07/01/20-02/28/25
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Thomas J. Montine, MD, PhD
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Laboratory Investigation Alzheimer's & Dementia
Patents:
1.
NONE
Publishing Royalties:
1.
UpToDate chapter on Neuropathology for Alzheimer's and and Lewy Body Diseases
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Michael J. Fox Foundation Farmer Family Foundation
Stock/stock Options/board of Directors Compensation:
1.
Stock options in a start up company named
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jan Aasly, MD
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Parkinson's disease;
Patents:
1.
Patent for LRRK2 G2019S
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH, U01 NS091272, co-Investigator (before 2020) / PI (since 2020), 2016-2021; (2) NIH, R01 AG056711, co-Investigator (before 2020) / PI (since 2020), 2017-2022; (3) NIH, R21 NS104511, co-Investigator (before 2020) / PI (since 2020), 2018-2021; (4) NIH, R01 AG061383, PI, 2019-2024; (5) NIH, RF1 AG068406, PI, 2020-2024; (6) NIH, R21 AG060142, co-Investigator (before 2020) / PI (since 2020), 2019-2021.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jing Zhang, MD, PhD
From 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.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH, U01 NS091272, PI (until Jan 2020), 2016-2021; (2) NIH, R01 AG056711, PI (until Jan 2020), 2017-2022; (3) NIH, R21 NS104511, PI (until Jan 2020), 2018-2021; (4) NIH, R21 MH118160, PI (until Jan 2020), 2018-2020.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Zhang [email protected] or Dr. Shi [email protected]
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.

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