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SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease
Cerebrospinal fluid (CSF) Aβ42 and tau protein levels are established diagnostic biomarkers of Alzheimer’s disease (AD). However, their inadequacy to represent clinical efficacy in drug trials indicates the need for new biomarkers. Sequential window acquisition of all theoretical fragment ion spectr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198522/ https://www.ncbi.nlm.nih.gov/pubmed/32366888 http://dx.doi.org/10.1038/s41598-020-64461-y |
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author | Park, Sun Ah Jung, Jin Myung Park, Jun Sung Lee, Jeong Ho Park, Bumhee Kim, Hyung Jun Park, Jeong-Ho Chae, Won Seok Jeong, Jee Hyang Choi, Seong Hye Baek, Je-Hyun |
author_facet | Park, Sun Ah Jung, Jin Myung Park, Jun Sung Lee, Jeong Ho Park, Bumhee Kim, Hyung Jun Park, Jeong-Ho Chae, Won Seok Jeong, Jee Hyang Choi, Seong Hye Baek, Je-Hyun |
author_sort | Park, Sun Ah |
collection | PubMed |
description | Cerebrospinal fluid (CSF) Aβ42 and tau protein levels are established diagnostic biomarkers of Alzheimer’s disease (AD). However, their inadequacy to represent clinical efficacy in drug trials indicates the need for new biomarkers. Sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based mass spectrometry (MS) is an advanced proteomic tool for large-scale, high-quality quantification. In this study, SWATH-MS showed that VGF, chromogranin-A, secretogranin-1, and opioid-binding protein/cell adhesion molecule were significantly decreased in 42 AD patients compared to 39 controls, whereas 14-3-3ζ was increased (FDR < 0.05). In addition, 16 other proteins showed substantial changes (FDR < 0.2). The expressions of the top 21 analytes were closely interconnected, but were poorly correlated with CSF Aβ42, tTau, and pTau181 levels. Logistic regression analysis and data mining were used to establish the best algorithm for AD, which created novel biomarker panels with high diagnostic value (AUC = 0.889 and 0.924) and a strong correlation with clinical severity (all p < 0.001). Targeted proteomics was used to validate their usefulness in a different cohort (n = 36) that included patients with other brain disorders (all p < 0.05). This study provides a list of proteins (and combinations thereof) that could serve as new AD biomarkers. |
format | Online Article Text |
id | pubmed-7198522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71985222020-05-08 SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease Park, Sun Ah Jung, Jin Myung Park, Jun Sung Lee, Jeong Ho Park, Bumhee Kim, Hyung Jun Park, Jeong-Ho Chae, Won Seok Jeong, Jee Hyang Choi, Seong Hye Baek, Je-Hyun Sci Rep Article Cerebrospinal fluid (CSF) Aβ42 and tau protein levels are established diagnostic biomarkers of Alzheimer’s disease (AD). However, their inadequacy to represent clinical efficacy in drug trials indicates the need for new biomarkers. Sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based mass spectrometry (MS) is an advanced proteomic tool for large-scale, high-quality quantification. In this study, SWATH-MS showed that VGF, chromogranin-A, secretogranin-1, and opioid-binding protein/cell adhesion molecule were significantly decreased in 42 AD patients compared to 39 controls, whereas 14-3-3ζ was increased (FDR < 0.05). In addition, 16 other proteins showed substantial changes (FDR < 0.2). The expressions of the top 21 analytes were closely interconnected, but were poorly correlated with CSF Aβ42, tTau, and pTau181 levels. Logistic regression analysis and data mining were used to establish the best algorithm for AD, which created novel biomarker panels with high diagnostic value (AUC = 0.889 and 0.924) and a strong correlation with clinical severity (all p < 0.001). Targeted proteomics was used to validate their usefulness in a different cohort (n = 36) that included patients with other brain disorders (all p < 0.05). This study provides a list of proteins (and combinations thereof) that could serve as new AD biomarkers. Nature Publishing Group UK 2020-05-04 /pmc/articles/PMC7198522/ /pubmed/32366888 http://dx.doi.org/10.1038/s41598-020-64461-y Text en © The Author(s) 2020 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/. |
spellingShingle | Article Park, Sun Ah Jung, Jin Myung Park, Jun Sung Lee, Jeong Ho Park, Bumhee Kim, Hyung Jun Park, Jeong-Ho Chae, Won Seok Jeong, Jee Hyang Choi, Seong Hye Baek, Je-Hyun SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title | SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title_full | SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title_fullStr | SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title_full_unstemmed | SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title_short | SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease |
title_sort | swath-ms analysis of cerebrospinal fluid to generate a robust battery of biomarkers for alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198522/ https://www.ncbi.nlm.nih.gov/pubmed/32366888 http://dx.doi.org/10.1038/s41598-020-64461-y |
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