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

Alzheimers Dement. 2023 Dec;19(12):5755-5764. doi: 10.1002/alz.13382. Epub 2023 Jul 12.

Abstract

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 Aβ isoforms predict cognitive impairment.

Methods: Plasma 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.

Results: Discovery 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.

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.

Keywords: Alzheimer disease; Aβ; Down syndrome; biomarker; plasma; tau.

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides
  • Biomarkers
  • Cognition
  • Cognitive Dysfunction*
  • Cross-Sectional Studies
  • Down Syndrome*
  • Humans
  • Peptide Fragments
  • tau Proteins

Substances

  • tau Proteins
  • Biomarkers
  • Amyloid beta-Peptides
  • Peptide Fragments