Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden
Alzheimer’s & Dementia | May 15, 2023
Juan Lantero-Rodriguez, Cécile Tissot, Anniina Snellman, Stijn Servaes, Andrea L. Benedet, Nesrine Rahmouni, Laia Montoliu-Gaya, Joseph Therriault, Wagner S. Brum, Jenna Stevenson, Firoza Z. Lussier, Gleb Bezgin, Arthur C. Macedo, Mira Chamoun, Sulantha S. Mathotaarachi, Tharick A. Pascoal, Nicholas J. Ashton, Henrik Zetterberg, Pedro Rosa Neto, Kaj Blennow
Alzheimers Dement. 2023
This study was performed using Simoa Homebrew assay(s).
Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed.
We measured cerebrospinal fluid (CSF) and plasma concentrations of N-terminal tau fragments (NTA-tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments.
CSF and plasma NTA-tau concentrations were specifically increased in cognitively impaired Aβ-positive groups. CSF and plasma NTA-tau concentrations displayed stronger correlations with tau PET than with Aβ PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA-tau are preferentially associated with tau pathology. Moreover, plasma NTA-tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer’s disease (AD) spectrum.
NTA-tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials.
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