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CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Despite recent advances in fluid biomarker research in Alzheimer’s disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specifi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800273/ https://www.ncbi.nlm.nih.gov/pubmed/36424467 http://dx.doi.org/10.1038/s41591-022-02075-9 |
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author | Horie, Kanta Barthélemy, Nicolas R. Spina, Salvatore VandeVrede, Lawren He, Yingxin Paterson, Ross W. Wright, Brenton A. Day, Gregory S. Davis, Albert A. Karch, Celeste M. Seeley, William W. Perrin, Richard J. Koppisetti, Rama K. Shaikh, Faris Lago, Argentina Lario Heuer, Hilary W. Ghoshal, Nupur Gabelle, Audrey Miller, Bruce L. Boxer, Adam L. Bateman, Randall J. Sato, Chihiro |
author_facet | Horie, Kanta Barthélemy, Nicolas R. Spina, Salvatore VandeVrede, Lawren He, Yingxin Paterson, Ross W. Wright, Brenton A. Day, Gregory S. Davis, Albert A. Karch, Celeste M. Seeley, William W. Perrin, Richard J. Koppisetti, Rama K. Shaikh, Faris Lago, Argentina Lario Heuer, Hilary W. Ghoshal, Nupur Gabelle, Audrey Miller, Bruce L. Boxer, Adam L. Bateman, Randall J. Sato, Chihiro |
author_sort | Horie, Kanta |
collection | PubMed |
description | Despite recent advances in fluid biomarker research in Alzheimer’s disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau(275) and MTBR-tau(282)) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPT and AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPT and AD compared to control and other FTLD-tau (for example, Pick’s disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau(275) and MTBR-tau(282) may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs. |
format | Online Article Text |
id | pubmed-9800273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-98002732022-12-31 CSF tau microtubule-binding region identifies pathological changes in primary tauopathies Horie, Kanta Barthélemy, Nicolas R. Spina, Salvatore VandeVrede, Lawren He, Yingxin Paterson, Ross W. Wright, Brenton A. Day, Gregory S. Davis, Albert A. Karch, Celeste M. Seeley, William W. Perrin, Richard J. Koppisetti, Rama K. Shaikh, Faris Lago, Argentina Lario Heuer, Hilary W. Ghoshal, Nupur Gabelle, Audrey Miller, Bruce L. Boxer, Adam L. Bateman, Randall J. Sato, Chihiro Nat Med Article Despite recent advances in fluid biomarker research in Alzheimer’s disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau(275) and MTBR-tau(282)) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPT and AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPT and AD compared to control and other FTLD-tau (for example, Pick’s disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau(275) and MTBR-tau(282) may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs. Nature Publishing Group US 2022-11-24 2022 /pmc/articles/PMC9800273/ /pubmed/36424467 http://dx.doi.org/10.1038/s41591-022-02075-9 Text en © The Author(s) 2022 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 Horie, Kanta Barthélemy, Nicolas R. Spina, Salvatore VandeVrede, Lawren He, Yingxin Paterson, Ross W. Wright, Brenton A. Day, Gregory S. Davis, Albert A. Karch, Celeste M. Seeley, William W. Perrin, Richard J. Koppisetti, Rama K. Shaikh, Faris Lago, Argentina Lario Heuer, Hilary W. Ghoshal, Nupur Gabelle, Audrey Miller, Bruce L. Boxer, Adam L. Bateman, Randall J. Sato, Chihiro CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title | CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title_full | CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title_fullStr | CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title_full_unstemmed | CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title_short | CSF tau microtubule-binding region identifies pathological changes in primary tauopathies |
title_sort | csf tau microtubule-binding region identifies pathological changes in primary tauopathies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800273/ https://www.ncbi.nlm.nih.gov/pubmed/36424467 http://dx.doi.org/10.1038/s41591-022-02075-9 |
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