Plasma NT1-tau and A₄₂ correlate with age and cognitive function in two large Down syndrome cohorts

INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and A beta isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, A beta(37), A beta(40), and A beta(42) levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, A beta(42), and A beta(37:42) were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and A beta(42) decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.