Alzheimer's & dementia : the journal of the Alzheimer's Association
Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults
By Huang Y, Huang L, Cui L and 5 others.
Abstract
Introduction
Plasma phosphorylated tau (p-tau)217 is increasingly used to triage amyloid testing, but the biological and clinical meaning of discordant plasma p-tau217 and amyloid positron emission tomography (PET) results in cognitively normal adults remains uncertain.
Methods
We analyzed cognitively normal participants from the Chinese Preclinical Alzheimer's Disease Study (CPAS; n = 594) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 475). Amyloid PET positivity was defined as Centiloid ≥ 20. Cohort-specific p-tau217 positivity was defined using PET-anchored cutoffs with ≥ 0.90 specificity, yielding four p-tau/PET groups. Linear models assessed cross-sectional biomarker and cognitive differences; mixed-effects and Cox models assessed ADNI longitudinal Centiloid accumulation, cognitive trajectories, and clinical progression.