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

https://doi.org/10.1002/alz.13119

This study was performed using Simoa Homebrew assay(s).

Abstract

INTRODUCTION

Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed.

METHODS

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.

RESULTS

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.

DISCUSSION

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.