Evidence map›Paper›PMID 38839930›Full record

ArticleEMBO molecular medicine2024

Aggregation-resistant alpha-synuclein tetramers are reduced in the blood of Parkinson's patients.

Laura de Boni, Amber Wallis, Aurelia Hays Watson, Alejandro Ruiz-Riquelme, Louise-Ann Leyland, Thomas Bourinaris, Naomi Hannaway, Ullrich Wüllner, Oliver Peters, Josef Priller and 17 more

Abstract read
In one paragraph

Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. ZnJournal of the American Chemical Society · 2025
    Article
  8. Review
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

27 authors.

Laura de BoniUK Dementia Research Institute, University College London, London, W1T 7NF, UK.ORCID http://orcid.org/0000-0001-7785-482X
Amber WallisUK Dementia Research Institute, University College London, London, W1T 7NF, UK.
Aurelia Hays WatsonUK Dementia Research Institute, University College London, London, W1T 7NF, UK.
Alejandro Ruiz-RiquelmeUniversity of Santiago de Compostela, 15705, Santiago de Compostela, Galicia, Spain.ORCID http://orcid.org/0000-0001-6581-7132
Louise-Ann LeylandDementia Research Center, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
Thomas BourinarisDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Naomi HannawayDementia Research Center, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
Ullrich WüllnerGerman Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
Oliver PetersInstitute of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 12203, Berlin, Germany.
Josef PrillerGerman Center for Neurodegenerative Diseases (DZNE), 10117, Berlin, Germany.ORCID http://orcid.org/0000-0001-7596-0979
Björn H FalkenburgerGerman Center for Neurodegenerative Diseases (DZNE), 01307, Dresden, Germany.
Jens WiltfangGerman Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.ORCID http://orcid.org/0000-0003-1492-5330
Mathias BährGerman Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.
Inga ZerrGerman Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.
Katharina BürgerGerman Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany.
Robert PerneczkyGerman Center for Neurodegenerative Diseases (DZNE), 81377, Munich, Germany.ORCID http://orcid.org/0000-0003-1981-7435
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, 17489, Rostock, Germany.
Matthias LöhleGerman Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, 17489, Rostock, Germany.
Wiebke HermannGerman Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, 17489, Rostock, Germany.
Björn-Hendrik SchottGerman Center for Neurodegenerative Diseases (DZNE), 37075, Goettingen, Germany.ORCID http://orcid.org/0000-0002-8237-4481
Kathrin BrockmannGerman Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
Annika SpottkeDepartment of Neurology, University Hospital Bonn, 53127, Bonn, Germany.
Katrin HausteinDepartment of Neurology, University Hospital Bonn, 53127, Bonn, Germany.
Peter BreuerDepartment of Neurology, University Hospital Bonn, 53127, Bonn, Germany.
Henry HouldenDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Rimona S WeilDementia Research Center, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.ORCID http://orcid.org/0000-0002-5092-6325
Tim BartelsUK Dementia Research Institute, University College London, London, W1T 7NF, UK. t.bartels@ucl.ac.uk.ORCID http://orcid.org/0000-0002-4071-5612

Funding

Utilization of proteomics and lipidomics to identify modifiers of LBDU54NS110435 · NINDS · MAYO CLINIC JACKSONVILLE · PI MCLEAN, PAMELA J · 2019 to 2023
$14.5M
Mechanisms of Synaptic Dysfunction in Parkinson s and Other Synuclein-Linked DiseasesR01NS078165 · NINDS · UNIVERSITY OF TEXAS AT AUSTIN · PI Jennifer Rebecca Morgan · 2012 to 2026
$5.5M
Elucidating the Biological Differences Between Distinct Fibrillar and Non-Fibrillar Alpha-Synuclein Inclusions in Human Stem-Cell ModelsR01NS109209 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KHURANA, VIKRAM · 2020 to 2024
$4.5M
Bundesministerium für Bildung und Forschung (BMBF) n.a.Chan Zuckerberg Collaborative Pairs Initiative Phase 2 n.a.Deutsche Forschungsgemeinschaft (DFG) n.a.Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) n.a.DRI n.a.Eisei pharmaceuticals n.a.ERDF n.a.Maria Zambrano Fellowship n.a.Ministerio de Ciencia e Innovación (MCIN) PID2021-1265840A-100NIH UK n.a.NINDS NIH HHS R01 NS078165NINDS NIH HHS R01 NS109209NINDS NIH HHS U54 NS110435Rosetrees Trust (Rosetrees) n.a.University Bonn n.a.University of Bonn n.a.US National Institute of Neurological Disorders nU54,2xR01Wellcome TrustWellcome Trust 205167
6 · The paper itself

Abstract

Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression.

Indexed as

alpha-SynucleinParkinson DiseaseAgedFemaleHumansMaleMiddle AgedProtein AggregatesProtein Multimerizationalpha-SynucleinProtein AggregatesSNCA protein, humanAlpha-synucleinBloodHumanParkinson’s diseaseTetramer

Identifiers

PMID38839930
PMCPMC11250827

What OpenQuestion holds

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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.