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Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy
There is a dire need for reliable biomarkers to solidify an early and accurate diagnosis of multiple system atrophy (MSA). We sought to compare the ability of emerging plasma markers in distinguishing MSA from its mimics and healthy controls in early disease stages, and to evaluate their performance...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017699/ https://www.ncbi.nlm.nih.gov/pubmed/36922526 http://dx.doi.org/10.1038/s41531-023-00481-5 |
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author | Guo, Yu Shen, Xue-Ning Huang, Shu-Yi Chen, Shu-Fen Wang, Hui-Fu Zhang, Wei Zhang, Ya-Ru Cheng, Wei Cui, Mei Dong, Qiang Yu, Jin-Tai |
author_facet | Guo, Yu Shen, Xue-Ning Huang, Shu-Yi Chen, Shu-Fen Wang, Hui-Fu Zhang, Wei Zhang, Ya-Ru Cheng, Wei Cui, Mei Dong, Qiang Yu, Jin-Tai |
author_sort | Guo, Yu |
collection | PubMed |
description | There is a dire need for reliable biomarkers to solidify an early and accurate diagnosis of multiple system atrophy (MSA). We sought to compare the ability of emerging plasma markers in distinguishing MSA from its mimics and healthy controls in early disease stages, and to evaluate their performance in detecting disease severity and brain atrophy. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, amyloid-β (Aβ)42, and Aβ40 were measured using ultrasensitive Simoa in early-stage patients with MSA (n = 73), spinocerebellar ataxia (SCA, n = 29), Parkinson’s disease (PD, n = 28), and healthy controls (n = 100). We observed that elevated NfL outperformed other biomarkers in distinguishing MSA and its subtypes (AUC = 0.9) versus controls. Intriguingly, when separating MSA from its mimics, increased GFAP (AUC = 0.717) in MSA-C and decreased Aβ40 (AUC = 0.807) in MSA-P best discriminated from SCA and PD respectively. Plasma levels were comparable between MSA-C and MSA-P and the differentiation by plasma index alone was poor. Combining plasma markers noticeably improved the discriminatory efficacy. Of note, among MSA patients, higher GFAP and NfL were correlated with the atrophy of brain regions vulnerable to MSA (e.g., cerebellum, pons, or putamen). They could also aggravate the severity of MSA, and this association was partially mediated by cerebral volumes. In contrast, no obvious associations of phosphorylated tau and Aβ with disease severity were observed. Collectively, plasma biomarkers, especially in combination, are useful to facilitate the discriminatory work-up of MSA at early stages. Moreover, NfL and GFAP may be promising biomarkers to monitor the disease severity of MSA. |
format | Online Article Text |
id | pubmed-10017699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100176992023-03-17 Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy Guo, Yu Shen, Xue-Ning Huang, Shu-Yi Chen, Shu-Fen Wang, Hui-Fu Zhang, Wei Zhang, Ya-Ru Cheng, Wei Cui, Mei Dong, Qiang Yu, Jin-Tai NPJ Parkinsons Dis Article There is a dire need for reliable biomarkers to solidify an early and accurate diagnosis of multiple system atrophy (MSA). We sought to compare the ability of emerging plasma markers in distinguishing MSA from its mimics and healthy controls in early disease stages, and to evaluate their performance in detecting disease severity and brain atrophy. Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau181, amyloid-β (Aβ)42, and Aβ40 were measured using ultrasensitive Simoa in early-stage patients with MSA (n = 73), spinocerebellar ataxia (SCA, n = 29), Parkinson’s disease (PD, n = 28), and healthy controls (n = 100). We observed that elevated NfL outperformed other biomarkers in distinguishing MSA and its subtypes (AUC = 0.9) versus controls. Intriguingly, when separating MSA from its mimics, increased GFAP (AUC = 0.717) in MSA-C and decreased Aβ40 (AUC = 0.807) in MSA-P best discriminated from SCA and PD respectively. Plasma levels were comparable between MSA-C and MSA-P and the differentiation by plasma index alone was poor. Combining plasma markers noticeably improved the discriminatory efficacy. Of note, among MSA patients, higher GFAP and NfL were correlated with the atrophy of brain regions vulnerable to MSA (e.g., cerebellum, pons, or putamen). They could also aggravate the severity of MSA, and this association was partially mediated by cerebral volumes. In contrast, no obvious associations of phosphorylated tau and Aβ with disease severity were observed. Collectively, plasma biomarkers, especially in combination, are useful to facilitate the discriminatory work-up of MSA at early stages. Moreover, NfL and GFAP may be promising biomarkers to monitor the disease severity of MSA. Nature Publishing Group UK 2023-03-15 /pmc/articles/PMC10017699/ /pubmed/36922526 http://dx.doi.org/10.1038/s41531-023-00481-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Guo, Yu Shen, Xue-Ning Huang, Shu-Yi Chen, Shu-Fen Wang, Hui-Fu Zhang, Wei Zhang, Ya-Ru Cheng, Wei Cui, Mei Dong, Qiang Yu, Jin-Tai Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title | Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title_full | Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title_fullStr | Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title_full_unstemmed | Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title_short | Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
title_sort | head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017699/ https://www.ncbi.nlm.nih.gov/pubmed/36922526 http://dx.doi.org/10.1038/s41531-023-00481-5 |
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