Combined plasma p-tau217 and tau-PET identify highest-risk preclinical Alzheimer's disease trajectories

Tau pathology biomarkers offer crucial prognostic indicators for neurodegeneration and cognitive decline in Alzheimer's disease (AD), essential for early patient stratification for disease-modifying interventions. Plasma p-tau217 indexes early tau pathophysiology, while [18F]flortaucipir PET (tau-PET) visual assessments reflect advanced neurofibrillary tangle pathology. This study aimed to identify how these combined biomarkers delineate distinct longitudinal trajectories of Aβ and tau accumulation, neurodegeneration, and cognitive decline in cognitively unimpaired individuals.

Researchers analyzed 330 cognitively unimpaired, Aβ-PET-positive participants from the A4 Study (mean age 72.2 years). Baseline assessments included plasma p-tau217 (positivity defined as ≥ 0.28 U/mL) and [18F]flortaucipir tau-PET visual assessments. Participants were stratified into four groups based on T1[-/+]T2[-/+] status. They were followed for 5.0 ± 1.7 years to track changes in Aβ-PET and tau-PET SUVR, MRI-measured gray-matter volume, and cognitive performance using ANCOVA and mixed-effects models.