Plasma NT1-tau and Aβ42 correlate with age and cognitive function in two large Down syndrome cohorts

Introduction: People with Down syndrome (DS) often develop Alzheimer 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: 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 the discovery cohort. In cross-sectional models, NT1-tau and A{beta}42 increased with age. NT1-tau predicted DLD scores. The discovery cohort linear model for NT1-tau predicted NT1-tau 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.