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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...

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Autores principales: Mengel, David, Mok, Tze How, Nihat, Akin, Liu, Wen, Rissman, Robert A., Galasko, Douglas, Zetterberg, Henrik, Mead, Simon, Collinge, John, Walsh, Dominic M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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