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, Alzheimer's Disease Neuroimaging Initiative, Mengjie Dong, Yan-Jiang Wang, Tengfei Guo
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.
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.