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NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression

Authors :
David Mengel
Tze How Mok
Akin Nihat
Wen Liu
Robert A. Rissman
Douglas Galasko
Henrik Zetterberg
Simon Mead
John Collinge
Dominic M. Walsh
Source :
Cells, Vol 10, Iss 12, p 3514 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

Language :
English
ISSN :
20734409
Volume :
10
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.bdd2558fdc456aa6bffb6167e61b9a
Document Type :
article
Full Text :
https://doi.org/10.3390/cells10123514