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α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357708/ https://www.ncbi.nlm.nih.gov/pubmed/33991233 http://dx.doi.org/10.1007/s00401-021-02324-0 |
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author | Dutta, Suman Hornung, Simon Kruayatidee, Adira Maina, Katherine N. del Rosario, Irish Paul, Kimberly C. Wong, Darice Y. Duarte Folle, Aline Markovic, Daniela Palma, Jose-Alberto Serrano, Geidy E. Adler, Charles H. Perlman, Susan L. Poon, Wayne W. Kang, Un Jung Alcalay, Roy N. Sklerov, Miriam Gylys, Karen H. Kaufmann, Horacio Fogel, Brent L. Bronstein, Jeff M. Ritz, Beate Bitan, Gal |
author_facet | Dutta, Suman Hornung, Simon Kruayatidee, Adira Maina, Katherine N. del Rosario, Irish Paul, Kimberly C. Wong, Darice Y. Duarte Folle, Aline Markovic, Daniela Palma, Jose-Alberto Serrano, Geidy E. Adler, Charles H. Perlman, Susan L. Poon, Wayne W. Kang, Un Jung Alcalay, Roy N. Sklerov, Miriam Gylys, Karen H. Kaufmann, Horacio Fogel, Brent L. Bronstein, Jeff M. Ritz, Beate Bitan, Gal |
author_sort | Dutta, Suman |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8357708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-83577082021-08-30 α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy Dutta, Suman Hornung, Simon Kruayatidee, Adira Maina, Katherine N. del Rosario, Irish Paul, Kimberly C. Wong, Darice Y. Duarte Folle, Aline Markovic, Daniela Palma, Jose-Alberto Serrano, Geidy E. Adler, Charles H. Perlman, Susan L. Poon, Wayne W. Kang, Un Jung Alcalay, Roy N. Sklerov, Miriam Gylys, Karen H. Kaufmann, Horacio Fogel, Brent L. Bronstein, Jeff M. Ritz, Beate Bitan, Gal Acta Neuropathol Original Paper 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. Springer Berlin Heidelberg 2021-05-15 2021 /pmc/articles/PMC8357708/ /pubmed/33991233 http://dx.doi.org/10.1007/s00401-021-02324-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Paper Dutta, Suman Hornung, Simon Kruayatidee, Adira Maina, Katherine N. del Rosario, Irish Paul, Kimberly C. Wong, Darice Y. Duarte Folle, Aline Markovic, Daniela Palma, Jose-Alberto Serrano, Geidy E. Adler, Charles H. Perlman, Susan L. Poon, Wayne W. Kang, Un Jung Alcalay, Roy N. Sklerov, Miriam Gylys, Karen H. Kaufmann, Horacio Fogel, Brent L. Bronstein, Jeff M. Ritz, Beate Bitan, Gal α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title | α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title_full | α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title_fullStr | α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title_full_unstemmed | α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title_short | α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson’s disease from multiple system atrophy |
title_sort | α-synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes parkinson’s disease from multiple system atrophy |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357708/ https://www.ncbi.nlm.nih.gov/pubmed/33991233 http://dx.doi.org/10.1007/s00401-021-02324-0 |
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