Cross‐Sectional and Longitudinal Diagnostic Performance of Plasma p‐tau217 and p‐tau217/Aβ42 in Alzheimer's Disease
Mingxing Jiang, Guoyu Lan, Jiayi Zhu, Laihong Zhang, Anqi Li, Zhengbo He, Yalin Zhu, Xin Zhou, Li Liang, Na Gao, Pan Sun, Yue Cai, Xiang Fan, Xuhui Chen, Dai Shi, Zhen Liu, Qingyong Wang, Guanxun Cheng, Lu Wang, , Mengjie Dong, Yan‐Jiang Wang, Tengfei GuoObjective
Recent studies suggest that combining plasma phosphorylated tau (p‐tau) with β ‐amyloid (A β ) may improve diagnosis accuracy for Alzheimer's disease (AD). However, the cross‐sectional and longitudinal concordance of these markers with A β 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 A β , 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 A β ‐PET imaging. Longitudinal data were available for 285 Alzheimer's Disease Neuroimaging Initiative participants. Plasma p‐tau181, p‐tau217, A β 42, and A β 40 were measured on different analytical platforms. Diagnostic performance for A β ‐PET positivity was assessed using a two‐cutoff approach.
Results
Combining plasma p‐tau with A β 42 or the A β 42/40 ratio reduced the intermediate zone. Notably, p‐tau217/A β 42 showed stronger agreement with A β ‐PET positivity than p‐tau217 alone. Among individuals classified as p‐tau217/A β 42 positive but p‐tau217 intermediate, 57.1 to 83.3% were A β ‐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/A β 42 were A β ‐PET positive and A β ‐PET negative, respectively. Critically, 69.7 to 75.8% of Non‐positive to Positive cases defined by p‐tau217/A β 42 were A β ‐PET positive.
Interpretation
These findings provide novel insights into the cross‐sectional and longitudinal diagnostic performance of plasma p‐tau217/A β 42 in AD. To be specific, plasma p‐tau217/A β 42 can reduce the intermediate zone and improve agreement with A β ‐PET positivity, and longitudinal p‐tau217/A β 42 monitoring is particularly informative for identifying A β ‐PET–positive patients who were p‐tau217/A β 42 negative or intermediate at baseline and were misclassified as low risk of AD. ANN NEUROL 2026