Evidence map›Paper›PMID 33991233›Full record

ArticleActa neuropathologica2021

α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy.

Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N Maina, Irish Del Rosario, Kimberly C Paul, Darice Y Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma and 13 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 109 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 6 pooled it
12.4field-weighted citation impact, top 1% 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

109 citing papers in PubMed, 6 syntheses or guidelines pooled it, 154 citations in OpenAlex.

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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 2 countries.

Suman DuttaDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Simon HornungDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Adira KruayatideeDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Katherine N MainaDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Irish Del RosarioDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
Kimberly C PaulDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
Darice Y WongDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Aline Duarte FolleDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
Daniela MarkovicDepartment of Medicine, Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Jose-Alberto PalmaDepartment of Neurology, Dysautonomia Center, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University School of Medicine, New York, NY, 10016, USA.
Geidy E SerranoBanner Sun Health Research Institute, Sun City, AZ, 85351, USA.
Charles H AdlerMayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
Susan L PerlmanDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Wayne W PoonInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697, USA.
Un Jung KangDepartment of Neurology, Dysautonomia Center, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University School of Medicine, New York, NY, 10016, USA.
Roy N AlcalayDepartment of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, 10032, USA.
Miriam SklerovDepartment of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Karen H GylysSchool of Nursing, University of California, Los Angeles, CA, 90095, USA.
Horacio KaufmannDepartment of Neurology, Dysautonomia Center, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University School of Medicine, New York, NY, 10016, USA.
Brent L FogelDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Jeff M BronsteinDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Beate RitzDepartment of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
Gal BitanDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. gbitan@mednet.ucla.edu.ORCID 0000-0001-7046-3754
University of California, Los Angeles · USDysautonomia Foundation · USBanner Sun Health Research Institute · USColumbia University · USMayo Clinic in Arizona · USUniversity of California, Irvine · USUniversity of North Carolina at Chapel Hill · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI ALEXANDER, GENE E · 2001 to 2020
$32.5M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI Nicholas Ashton · 2021 to 2026
$24.9M
Training CoreU54NS065736 · NINDS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FREEMAN, ROY · 2009 to 2018
$11.6M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
PARKINSON'S DISEASES SUSCEPTIBILITY GENES AND PESTICIDESR01ES010544 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2000 to 2015
$5.7M
Microbiome, Pesticides and Parkinsons in LatinosR01ES031106 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2020 to 2025
$3.8M
A futility trial of sirolimus in multiple system atrophyR01NS107596 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KAUFMANN, HORACIO, PALMA CARAZO, JOSE ALBERTO · 2018 to 2020
$2.4M
Rare and Novel Genetic Variation in the Pathogenesis of Cerebellar AtaxiaR01NS082094 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGEL, BRENT LINDEN · 2013 to 2017
$1.7M
The role of glucocerebrosidase in Parkinson's diseaseK02NS080915 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALCALAY, ROY · 2012 to 2016
$905k
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NIEHS NIH HHS R01 ES010544NIEHS NIH HHS R01 ES031106NINDS NIH HHS K02 NS080915NINDS NIH HHS R01 NS082094NINDS NIH HHS R01 NS107596NINDS NIH HHS U24 NS072026NINDS NIH HHS U54 NS065736
6 · The paper itself

Abstract

The diagnosis of Parkinson's disease (PD) and atypical parkinsonian syndromes is difficult due to the lack of reliable, easily accessible biomarkers. Multiple system atrophy (MSA) is a synucleinopathy whose symptoms often overlap with PD. Exosomes isolated from blood by immunoprecipitation using CNS markers provide a window into the brain's biochemistry and may assist in distinguishing between PD and MSA. Thus, we asked whether α-synuclein (α-syn) in such exosomes could distinguish among healthy individuals, patients with PD, and patients with MSA. We isolated exosomes from the serum or plasma of these three groups by immunoprecipitation using neuronal and oligodendroglial markers in two independent cohorts and measured α-syn in these exosomes using an electrochemiluminescence ELISA. In both cohorts, α-syn concentrations were significantly lower in the control group and significantly higher in the MSA group compared to the PD group. The ratio between α-syn concentrations in putative oligodendroglial exosomes compared to putative neuronal exosomes was a particularly sensitive biomarker for distinguishing between PD and MSA. Combining this ratio with the α-syn concentration itself and the total exosome concentration, a multinomial logistic model trained on the discovery cohort separated PD from MSA with an AUC = 0.902, corresponding to 89.8% sensitivity and 86.0% specificity when applied to the independent validation cohort. The data demonstrate that a minimally invasive blood test measuring α-syn in blood exosomes immunoprecipitated using CNS markers can distinguish between patients with PD and patients with MSA with high sensitivity and specificity. Future optimization and validation of the data by other groups would allow this strategy to become a viable diagnostic test for synucleinopathies.

Indexed as

AdultAgedAged, 80 and overalpha-SynucleinArea Under CurveBiomarkersCohort StudiesDiagnosis, DifferentialEnzyme-Linked Immunosorbent AssayExosomesFemaleHealthy VolunteersHumansImmunoprecipitationMaleMiddle Agedalpha-SynucleinBiomarkersSNCA protein, humanBiofluidBiomarkerExtracellular vesiclesSynucleinopathy

Identifiers

PMID33991233
PMCPMC8357708
OpenAlexW3162121356

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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.