Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden

Abstract

<p>INTRODUCTION<br></p><p>Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed.<br></p><p> METHODS<br></p><p>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. <br></p><p>RESULTS<br></p><p>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. <br></p><p>DISCUSSION<br></p><p>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. <br></p><p>HIGHLIGHTS<br></p><p>An assay for detecting N-terminal tau fragments (NTA-tau) in plasma and CSF was evaluated.<br></p><p>NTA-tau is more closely associated with tau PET than amyloid PET or neurodegeneration.<br></p><p>NTA-tau can successfully track in vivo tau deposition across the AD continuum.<br></p><p>Plasma NTA-tau increased over time only in cognitively impaired amyloid-beta positive individuals.</p>