INTRODUCTION
Longitudinal diagnostic and prognostic validity of plasma phosphorylated tau217 (p-tau217) in Alzheimer's disease (AD) remains uncertain.
METHODS
In this multi-cohort study of 2117 individuals, we established baseline plasma p-tau217 thresholds for amyloid-β-positron emission tomography (Aβ-PET) and assessed their longitudinal classification stability and prognostic relevance for AD-related outcomes.
RESULTS
Baseline-defined cutoffs achieved high and sustained accuracy (86%-95%) for Aβ-PET positivity over up to 5 years of follow-up. Longitudinally, most p-tau217-positive individuals remained stable (93%-98%), whereas the intermediate zone group progressed more to positive (44%-78%) than p-tau217-negative individuals (4%-21%). Participants with stable-positive and progress-to-positive p-tau217 profiles more frequently exhibited Aβ abnormalities (90%-100% and 64%-96%, respectively) and experienced accelerated tau accumulation, hippocampal atrophy, and incident dementia compared to those with a stable-negative p-tau217 profile.
DISCUSSION
These findings support the high stability and Aβ-PET classification performance of longitudinal plasma p-tau217 monitoring in AD, providing a scalable tool for risk stratification and disease monitoring.
Guo-Yu Lan, Wang Liao, Ming-Xing Jiang et al.· Alzheimer's & Dementia· 0 citations
OBJECTIVE
Recent studies suggest that combining plasma phosphorylated tau (p-tau) with β-amyloid (Aβ) may improve diagnosis accuracy for Alzheimer's disease (AD). However, the cross-sectional and longitudinal concordance of these markers with Aβ positron emission tomography (PET) positivity remains incompletely understood. This study aimed to evaluate the diagnostic performance of plasma p-tau, alone and in combination with plasma Aβ, in AD.
METHODS
We included 326 participants from the Alzheimer's Disease Neuroimaging Initiative and 357 Chinese older adults from the Greater-Bay-Area Healthy Aging Brain Study who underwent Aβ-PET imaging. Longitudinal data were available for 285 Alzheimer's Disease Neuroimaging Initiative participants. Plasma p-tau181, p-tau217, Aβ42, and Aβ40 were measured on different analytical platforms. Diagnostic performance for Aβ-PET positivity was assessed using a two-cutoff approach.
RESULTS
Combining plasma p-tau with Aβ42 or the Aβ42/40 ratio reduced the intermediate zone. Notably, p-tau217/Aβ42 showed stronger agreement with Aβ-PET positivity than p-tau217 alone. Among individuals classified as p-tau217/Aβ42 positive but p-tau217 intermediate, 57.1 to 83.3% were Aβ-PET positive. Longitudinally, most Stable Positive (88.0-96.1%) and Stable Negative (89.4-90.9%) cases defined by p-tau217 or p-tau217/Aβ42 were Aβ-PET positive and Aβ-PET negative, respectively. Critically, 69.7 to 75.8% of Non-positive to Positive cases defined by p-tau217/Aβ42 were Aβ-PET positive.
INTERPRETATION
These findings provide novel insights into the cross-sectional and longitudinal diagnostic performance of plasma p-tau217/Aβ42 in AD. To be specific, plasma p-tau217/Aβ42 can reduce the intermediate zone and improve agreement with Aβ-PET positivity, and longitudinal p-tau217/Aβ42 monitoring is particularly informative for identifying Aβ-PET-positive patients who were p-tau217/Aβ42 negative or intermediate at baseline and were misclassified as low risk of AD. ANN NEUROL 2026.
Mingxing Jiang, Guoyu Lan, Jiayi Zhu et al.· Annals of Neurology· 0 citations