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

Abstract

INTRODUCTIONPeople 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 Aβ isoforms predict cognitive impairment.METHODSPlasma NT1‐tau, Aβ37, Aβ40, and Aβ42 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.RESULTSDiscovery cohort linear mixed models for NT1‐tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross‐sectional models, NT1‐tau increased and Aβ42 decreased with age. NT1‐tau predicted cognitive and functional scores. The discovery cohort linear model for NT1‐tau predicted levels in the validation cohort.DISCUSSIONNT1‐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.