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 (A beta) 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 A beta-positive groups. CSF and plasma NTA-tau concentrations displayed stronger correlations with tau PET than with A beta 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.

HIGHLIGHTS

An assay for detecting N-terminal tau fragments (NTA-tau) in plasma and CSF was evaluated.

NTA-tau is more closely associated with tau PET than amyloid PET or neurodegeneration.

NTA-tau can successfully track in vivo tau deposition across the AD continuum.

Plasma NTA-tau increased over time only in cognitively impaired amyloid-beta positive individuals.