Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
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
_version_ 1784861260566757376
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
work_keys_str_mv AT horiekanta csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT barthelemynicolasr csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT spinasalvatore csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT vandevredelawren csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT heyingxin csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT patersonrossw csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT wrightbrentona csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT daygregorys csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT davisalberta csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT karchcelestem csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT seeleywilliamw csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT perrinrichardj csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT koppisettiramak csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT shaikhfaris csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT lagoargentinalario csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT heuerhilaryw csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT ghoshalnupur csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT gabelleaudrey csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT millerbrucel csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT boxeradaml csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT batemanrandallj csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies
AT satochihiro csftaumicrotubulebindingregionidentifiespathologicalchangesinprimarytauopathies