Evidence map›Paper›PMID 32557811›Full record

ArticleAnnals of neurology2020

Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies.

Wolfgang Singer, Ann M Schmeichel, Mohammad Shahnawaz, James D Schmelzer, Bradley F Boeve, David M Sletten, Tonette L Gehrking, Jade A Gehrking, Anita D Olson, Rodolfo Savica and 3 more

Abstract read
In one paragraph

Article in Annals of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

91 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2022
    Pooled it
  4. Cutaneous alpha-synuclein deposition informs autonomic function in individuals with early-stage multiple system atrophy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026
    Article
  5. Multiple system atrophy: cure and care.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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31 more citing papers are in PubMed but not listed here.

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

13 authors.

Wolfgang SingerDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0003-1263-6850
Ann M SchmeichelDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Mohammad ShahnawazMitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.
James D SchmelzerDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
David M SlettenDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Tonette L GehrkingDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Jade A GehrkingDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Anita D OlsonDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Rodolfo SavicaDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Mariana D SuarezDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Claudio SotoMitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas McGovern Medical School at Houston, Houston, Texas, USA.
Phillip A LowDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.ORCID 0000-0002-5386-4764

Funding

Mayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PANKRATZ, V. SHANE · 1999 to 2018
$36.9M
Longitudinal Imaging Biomarkers of Prodromal DLBU01NS100620 · NINDS · MAYO CLINIC ROCHESTER · PI Bradley F Boeve, KEJAL KANTARCI · 2017 to 2026
$19.2M
Synucleinopathies – Novel Targets in Early Diagnosis, Pathophysiology, and Therapeutic ApproachR01NS092625 · NINDS · MAYO CLINIC ROCHESTER · PI SINGER, WOLFGANG, VEMURI, PRASHANTHI · 2015 to 2025
$6.6M
Misfolded Protein Aggregates in HIV infectionR01AG061069 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ARDUINO, ROBERTO CLAUDIO, SOTO, CLAUDIO · 2018 to 2022
$3.5M
Comprehensive diagnosis of Alzheimer's disease by detection of misfolded oligomers in biological fluidsRF1AG055053 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI SOTO, CLAUDIO · 2019 to 2019
$2.9M
LISPRO, an ionic cocrystal of lithium, as a potential novel treatment for Alzheimer's diseaseR01AG050253 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI TAN, JUN · 2016 to 2019
$1.5M
Differential Approach to the Postural Tachycardia SyndromeK23NS075141 · NINDS · MAYO CLINIC ROCHESTER · PI SINGER, WOLFGANG · 2012 to 2016
$872k
Phase 1 Study of Autologous Mesenchymal Stem Cell in Multiple System AtrophyR01FD004789 · FDA · MAYO CLINIC ROCHESTER · PI LOW, PHILLIP A · 2014 to 2016
$600k
FDA HHS R01 FD004789NCATS NIH HHS UL1 TR000135NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG050253NIA NIH HHS R01 AG061069NIA NIH HHS RF1 AG055053NINDS NIH HHS K23 NS075141NINDS NIH HHS R01 NS092625NINDS NIH HHS U01 NS100620
6 · The paper itself

Abstract

objectiveTo explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings with Lewy body synucleinopathies.

methodsIn a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14), we utilized enzyme-linked immunosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF. We confirmed findings in a separate prospectively enrolled cohort of patients with early MSA (n = 38), Parkinson disease (PD, n = 16), and dementia with Lewy bodies (DLB, n = 13), and CON subjects (n = 15).

resultsIn the discovery cohort, NFL was markedly elevated in MSA patients, with perfect separation from CON. αSyn-PMCA was nonreactive in all CON, whereas all MSA samples were positive. In the confirmatory cohort, NFL again perfectly separated MSA from CON, and was significantly lower in PD and DLB compared to MSA. PMCA was again nonreactive in all CON, and positive in all but 2 MSA cases. All PD and all but 2 DLB samples were also positive for αSyn aggregates but with markedly different reaction kinetics from MSA; aggregation occurred later, but maximum fluorescence was higher, allowing for perfect separation of reactive samples between MSA and Lewy body synucleinopathies.

interpretationNFL and αSyn oligomers in CSF faithfully differentiate early MSA not only from CON but also from Lewy body synucleinopathies. The findings support the role of these markers as diagnostic biomarkers, and have important implications for understanding pathophysiologic mechanisms underlying the synucleinopathies. ANN NEUROL 2020;88:503-512.

Indexed as

Agedalpha-SynucleinBiomarkersDiagnosis, DifferentialFemaleHumansLewy Body DiseaseMaleMiddle AgedMultiple System AtrophyNeurofilament ProteinsParkinson Diseasealpha-SynucleinBiomarkersneurofilament protein LNeurofilament Proteins

Identifiers

PMID32557811
PMCPMC7719613

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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.