Evidence map›Paper›PMID 39475636›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

Measurement of α-synuclein as protein cargo in plasma extracellular vesicles.

Tal Gilboa, Dmitry Ter-Ovanesyan, Shih-Chin Wang, Sara Whiteman, George T Kannarkat, George M Church, Alice S Chen-Plotkin, David R Walt

Erratum issuedAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. 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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

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  14. Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Tal Gilboa *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.ORCID 0000-0001-8172-7786
Dmitry Ter-Ovanesyan *Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.ORCID 0000-0002-1134-0073
Shih-Chin WangWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
Sara WhitemanWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
George T KannarkatDepartment of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
George M ChurchWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
Alice S Chen-PlotkinDepartment of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
David R WaltWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.ORCID 0000-0002-5524-7348

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI JASON H KARLAWISH · 2021 to 2026
$24.8M
Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · NIA · UNIVERSITY OF PENNSYLVANIA · PI VIRGINIA M LEE · 2024 to 2026
$15.2M
Understanding biomarkers of cognitive decline in Lewy body diseasesR37NS115139 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI ALICE S CHEN-PLOTKIN · 2024 to 2026
$2.2M
Determining the Origin and Pathogenicity of Plasma-Derived Alpha-SynucleinStrainsK08NS133286 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI George T Kannarkat · 2024 to 2026
$694k
Chan Zuckerberg Initiative (CZI) NDCNMichael J. Fox Foundation for Parkinson's Research (MJFF) 2021A017224NIA NIH HHS P01 AG084497NIA NIH HHS P30 AG072979NIEHS NIH HHS P30 ES013508NINDS NIH HHS K08 NS133286NINDS NIH HHS R37 NS115139
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are released by all cells and hold great promise as a class of biomarkers. This promise has led to increased interest in measuring EV proteins from both total EVs as well as brain-derived EVs in plasma. However, measuring cargo proteins in EVs has been challenging because EVs are present at low levels, and EV isolation methods are imperfect at separating EVs from free proteins. Thus, knowing whether a protein measured after EV isolation is truly inside EVs is difficult. In this study, we developed methods to measure whether a protein is inside EVs and quantify the ratio of a protein in EVs relative to total plasma. To achieve this, we combined a high-yield size-exclusion chromatography protocol with an optimized protease protection assay and Single Molecule Array (Simoa) digital enzyme-linked immunoassays (ELISAs) for ultrasensitive measurement of proteins inside EVs. We applied these methods to analyze α-synuclein and confirmed that a small fraction of the total plasma α-synuclein is inside EVs. Additionally, we developed a highly sensitive Simoa assay for phosphorylated α-synuclein (phosphorylated at the Ser129 residue). We found enrichment in the phosphorylated α-synuclein to total α-synuclein ratio inside EVs relative to outside EVs. Finally, we applied the methods we developed to measure total and phosphorylated α-synuclein inside EVs from Parkinson's disease and Lewy body dementia patient samples. This work provides a framework for determining the levels of proteins in EVs and represents an important step in the development of EV diagnostics for diseases of the brain, as well as other organs.

Indexed as

alpha-SynucleinExtracellular VesiclesParkinson DiseaseBiomarkersBrainChromatography, GelEnzyme-Linked Immunosorbent AssayHumansPhosphorylationalpha-SynucleinBiomarkersalpha synucleinbiomarkerexosomesextracellular vesiclesParkinson’s Disease

Identifiers

PMID39475636
PMCPMC11551346

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.