Evidence map›Paper›PMID 32273329›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2020

Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism.

Cheng Jiang, Franziska Hopfner, Antigoni Katsikoudi, Robert Hein, Candan Catli, Samuel Evetts, Yongzhi Huang, Hong Wang, John W Ryder, Gregor Kuhlenbaeumer and 7 more

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

Article in Journal of neurology, neurosurgery, and psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 6 pooled it
13.4field-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

173 citing papers in PubMed, 6 syntheses or guidelines pooled it, 271 citations in OpenAlex.

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113 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

17 authors at 5 institutions in 4 countries.

Cheng JiangNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Franziska HopfnerNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Antigoni KatsikoudiNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Robert HeinDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, United Kingdom.
Candan CatliDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, United Kingdom.
Samuel EvettsNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Yongzhi HuangNuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.ORCID 0000-0002-2503-1589
Hong WangLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
John W RyderLilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
Gregor KuhlenbaeumerDepartment of Neurology, Christian-Albrechts-University, Kiel, Germany.
Guenther DeuschlDepartment of Neurology, Christian-Albrechts-University, Kiel, Germany.
Alessandro PadovaniDepartment of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.
Daniela BergDepartment of Neurology, Christian-Albrechts-University, Kiel, Germany.
Barbara BorroniDepartment of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.ORCID 0000-0001-9340-9814
Michele T HuNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Jason J DavisDepartment of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, United Kingdom.
George K TofarisNuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK george.tofaris@ndcn.ox.ac.uk.ORCID 0000-0002-9252-5933
John Radcliffe Hospital · GBChristian-Albrechts-Universität zu Kiel · DEUniversity of Oxford · GBEli Lilly (United States) · USUniversity of Brescia · IT

Funding

Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MR/L023784/1Medical Research Council MR/M024962/1Parkinson's UK J-0901Wellcome Trust
6 · The paper itself

Abstract

objectiveParkinson's disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson's from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson's disease, multiple system atrophy and other proteinopathies.

methodsWe performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson's and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.

resultsMean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson's disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson's disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson's disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson's disease progression.

conclusionsIncreased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson's disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson's disease from atypical parkinsonism.

Indexed as

AgedAged, 80 and overBiomarkersCross-Sectional StudiesDiagnosis, DifferentialExosomesFemaleHumansMaleMiddle AgedMultiple System AtrophyNeuronsParkinson DiseaseParkinsonian DisordersBiomarkers

Identifiers

PMID32273329
PMCPMC7361010
OpenAlexW3013209986

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.