Plasma NT1-tau and Aβ42correlate with age and cognitive function in two large Down syndrome cohorts

Structured Abstract 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 Aβ isoforms predict cognitive impairment. Methods Plasma NT1-tau, Aβ 37 , Aβ 40 , and Aβ 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, Aβ 42, and Aβ 37:42 were significant for age, there was no main effect of time in the discovery cohort. In cross-sectional models, NT1-tau and Aβ 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.