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

Cells

Henrik Zetterberg¹  Robert A. Rissman²  Wen Liu³  Dominic M. Walsh³  David Mengel³  Tze How Mok⁴  Simon Mead⁴  Akin Nihat⁴  John Collinge⁴  Douglas Galasko⁵ 

[1] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA;Laboratory for Neurodegenerative Research, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA;MRC Prion Unit at UCL, UCL Institute of Prion Diseases and NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCL Hospitals NHS Foundation Trust, London W1W 7FF, UK;VA San Diego Healthcare System, La Jolla, CA 92161, USA;

关键词: Alzheimer’s disease;    biomarker;    blood;    cerebrospinal fluid;    neurodegeneration;    neurofilament light chain;   

DOI  :  10.3390/cells10123514

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown