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NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression
This study investigates the diagnostic and prognostic potential of different forms of tau in biofluids from patients with Creutzfeldt-Jakob disease (CJD). Extracellular tau, which is molecularly heterogeneous, was measured using ultra-sensitive custom-made Simoa assays for N-terminal (NT1), mid-regi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700417/ https://www.ncbi.nlm.nih.gov/pubmed/34944022 http://dx.doi.org/10.3390/cells10123514 |
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author | Mengel, David Mok, Tze How Nihat, Akin Liu, Wen Rissman, Robert A. Galasko, Douglas Zetterberg, Henrik Mead, Simon Collinge, John Walsh, Dominic M. |
author_facet | Mengel, David Mok, Tze How Nihat, Akin Liu, Wen Rissman, Robert A. Galasko, Douglas Zetterberg, Henrik Mead, Simon Collinge, John Walsh, Dominic M. |
author_sort | Mengel, David |
collection | PubMed |
description | This study investigates the diagnostic and prognostic potential of different forms of tau in biofluids from patients with Creutzfeldt-Jakob disease (CJD). Extracellular tau, which is molecularly heterogeneous, was measured using ultra-sensitive custom-made Simoa assays for N-terminal (NT1), mid-region, and full-length tau. We assessed cross-sectional CSF and plasma from healthy controls, patients with Alzheimer’s disease (AD) and CJD patients. Then, we evaluated the correlation of the best-performing tau assay (NT1-tau) with clinical severity and functional decline (using the MRC Prion Disease Rating Scale) in a longitudinal CJD cohort (n = 145). In a cross-sectional study, tau measured in CSF with the NT1 and mid-region Simoa assays, separated CJD (n = 15) from AD (n = 18) and controls (n = 21) with a diagnostic accuracy (AUCs: 0.98–1.00) comparable to or better than neurofilament light chain (NfL; AUCs: 0.96–0.99). In plasma, NT1-measured tau was elevated in CJD (n = 5) versus AD (n = 15) and controls (n = 15). Moreover, in CJD plasma (n = 145) NT1-tau levels correlated with stage and rate of disease progression, and the effect on clinical progression was modified by the PRNP codon 129. Our findings suggest that plasma NT1-tau shows promise as a minimally invasive diagnostic and prognostic biomarker of CJD, and should be further investigated for its potential to monitor disease progression and response to therapies. |
format | Online Article Text |
id | pubmed-8700417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87004172021-12-24 NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression Mengel, David Mok, Tze How Nihat, Akin Liu, Wen Rissman, Robert A. Galasko, Douglas Zetterberg, Henrik Mead, Simon Collinge, John Walsh, Dominic M. Cells Article This study investigates the diagnostic and prognostic potential of different forms of tau in biofluids from patients with Creutzfeldt-Jakob disease (CJD). Extracellular tau, which is molecularly heterogeneous, was measured using ultra-sensitive custom-made Simoa assays for N-terminal (NT1), mid-region, and full-length tau. We assessed cross-sectional CSF and plasma from healthy controls, patients with Alzheimer’s disease (AD) and CJD patients. Then, we evaluated the correlation of the best-performing tau assay (NT1-tau) with clinical severity and functional decline (using the MRC Prion Disease Rating Scale) in a longitudinal CJD cohort (n = 145). In a cross-sectional study, tau measured in CSF with the NT1 and mid-region Simoa assays, separated CJD (n = 15) from AD (n = 18) and controls (n = 21) with a diagnostic accuracy (AUCs: 0.98–1.00) comparable to or better than neurofilament light chain (NfL; AUCs: 0.96–0.99). In plasma, NT1-measured tau was elevated in CJD (n = 5) versus AD (n = 15) and controls (n = 15). Moreover, in CJD plasma (n = 145) NT1-tau levels correlated with stage and rate of disease progression, and the effect on clinical progression was modified by the PRNP codon 129. Our findings suggest that plasma NT1-tau shows promise as a minimally invasive diagnostic and prognostic biomarker of CJD, and should be further investigated for its potential to monitor disease progression and response to therapies. MDPI 2021-12-13 /pmc/articles/PMC8700417/ /pubmed/34944022 http://dx.doi.org/10.3390/cells10123514 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mengel, David Mok, Tze How Nihat, Akin Liu, Wen Rissman, Robert A. Galasko, Douglas Zetterberg, Henrik Mead, Simon Collinge, John Walsh, Dominic M. NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title | NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title_full | NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title_fullStr | NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title_full_unstemmed | NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title_short | NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression |
title_sort | nt1-tau is increased in csf and plasma of cjd patients, and correlates with disease progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700417/ https://www.ncbi.nlm.nih.gov/pubmed/34944022 http://dx.doi.org/10.3390/cells10123514 |
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