Evidence map›Paper›PMID 33373501›Full record

ArticleAnnals of clinical and translational neurology2021

A rapid α-synuclein seed assay of Parkinson's disease CSF panel shows high diagnostic accuracy.

Christina D Orrù, Thong C Ma, Andrew G Hughson, Bradley R Groveman, Ankit Srivastava, Douglas Galasko, Rachel Angers, Patrick Downey, Karen Crawford, Samantha J Hutten and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 citations in OpenAlex.

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  10. 3,4-Dihydroxyphenylglycol levels separate multiple system atrophy from Parkinson disease with orthostatic hypotension.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 2 countries.

Christina D OrrùLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana.ORCID 0000-0001-7253-2944
Thong C MaDepartment of Neurology, New York University Grossman School of Medicine, New York, New York.
Andrew G HughsonLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana.
Bradley R GrovemanLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana.
Ankit SrivastavaLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana.
Douglas GalaskoDepartment of Neurosciences, University of California-San Diego, La Jolla, California.
Rachel AngersUCB Biopharma SRL, Braine l'Alleud, Belgium.
Patrick DowneyUCB Biopharma SRL, Braine l'Alleud, Belgium.
Karen CrawfordLaboratory of Neuro Imaging, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, California.
Samantha J HuttenMichael J. Fox Foundation, New York, New York.
Un Jung KangDepartment of Neurology, New York University Grossman School of Medicine, New York, New York.
Byron CaugheyLaboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana.ORCID 0000-0002-3928-6101
National Institute of Allergy and Infectious Diseases · USNew York University · USUCB Pharma (Belgium) · BEMichael J. Fox Foundation · USUniversity of California San Diego · USUniversity of Southern California · US

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
NINDS Biomarker RepositoryU24NS095871 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI TATIANA M. FOROUD · 2015 to 2026
$18.3M
Detection of PrionsZIAAI001086 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CAUGHEY, BYRON · 2009 to 2025
$18.1M
NIA NIH HHS U24 AG021886NINDS NIH HHS U24 NS095871
6 · The paper itself

Abstract

backgroundAssays that specifically measure α-synuclein seeding activity in biological fluids could revolutionize the diagnosis of Parkinson's disease. Recent improvements in α-synuclein real-time quaking-induced conversion assays of cerebrospinal fluid have dramatically reduced reaction times from 5-13 days down to 1-2 days.

objectiveTo test our improved assay against a panel of cerebrospinal fluid specimens from patients with Parkinson's disease and healthy controls from the MJ Fox Foundation/NINDS BioFIND collection.

methodsSpecimens collected from healthy controls and patients with clinically typical moderate-to-advanced Parkinson's disease were tested without prior knowledge of disease status. Correlative analyses between assay parameters and clinical measures were performed by an independent investigator.

resultsBioFIND samples gave positive signals in 105/108 (97%) Parkinson's disease cases versus 11/85 (13%) healthy controls. Receiver operating characteristic analyses of diagnosis of cases versus healthy controls gave areas under the curve of 95%. Beyond binary positive/negative determinations, only weak correlations were observed between various assay response parameters and Parkinson's disease clinical measures or other cerebrospinal fluid analytes. Of note, REM sleep behavioral disorder questionnaire scores correlated with the reaction times needed to reach 50% maximum fluorescence. Maximum fluorescence was inversely correlated with Unified Parkinson's Disease Rating Scale motor scores, which was driven by the patients without REM sleep behavioral disorder.

conclusionsOur improved α-synuclein seed amplification assay dramatically reduces the time needed to diagnose Parkinson's disease while maintaining the high-performance standards associated with previous α-synuclein seed assays, supporting the clinical utility of this assay for Parkinson's disease diagnosis.

Indexed as

Agedalpha-SynucleinBiological AssayBiomarkersCorrelation of DataFemaleHumansMaleMiddle AgedParkinson Diseasealpha-SynucleinBiomarkers

Identifiers

PMID33373501
PMCPMC7886040
OpenAlexW3116610736

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.