Wang Jun, Huang Shan, Lan Guoyu, Lai Yu-Jie, Wang Qing-Hua, Chen Yang, Xiao Zhong-Song, Chen Xiao, Bu Xian-Le, Liu Yu-Hui, Zeng Fan, Zhang Laihong, Li Anqi, Cai Yue, Sun Pan, He Zhengbo, Doré Vincent, Fripp Jurgen, Bourgeat Pierrick, Chen Qin, Yu Jin-Tai, Tang Yi, Zetterberg Henrik, Masters Colin L, Guo Tengfei, Wang Yan-Jiang
Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.
Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China.
Alzheimers Dement. 2025 Mar;21(3):e70038. doi: 10.1002/alz.70038.
This study was undertaken to evaluate the diagnostic performance of a novel plasma phosphorylated tau (p-tau) 217/amyloid beta (Aβ) 42 ratio test for Alzheimer's disease (AD).
The diagnostic performance of the Lumipulse G plasma p-tau217/Aβ42 ratio was evaluated using Aβ and tau positron emission tomography (PET) as reference standards in a clinic cohort (n = 391) and a community cohort (n = 121).
Plasma p-tau217/Aβ42 exhibited high performance for abnormal statuses of Aβ PET (area under the curve [AUC]: 0.963 to 0.966) and tau PET (AUC: 0.947 to 0.974), which were clinically equivalent to those of cerebrospinal fluid (CSF) p-tau181/Aβ42 and Aβ42/Aβ40 and higher than those of blood p-tau217, Aβ42/Aβ40, p-tau181, and p-tau181/Aβ42 in both clinic and community cohorts. Applying a two-cutoff approach improved the specificity without reducing sensitivity. The p-tau217/Aβ42 ratio had a lower intermediate percentage than p-tau217 alone in both clinic (10.6% vs 13.0%) and community (16.5% vs 31.4%) cohorts.
Plasma p-tau217/Aβ42 has high performance in detecting cerebral AD pathologies, thus offering a promising tool for clinical diagnosis and community screening of AD.
Lumipulse G plasma p-tau217 and the p-tau217/Aβ42 ratio accurately identified abnormal Aβ and tau PET statuses in both clinical and community cohorts. The performance of plasma p-tau217 and p-tau217/Aβ42 ratio were equivalent to CSF tests. Plasma p-tau217/Aβ42 ratio outperformed p-tau217 alone in identifying Aβ PET positivity, and this superiority is more obvious in the community cohort, suggesting an advantage in the early diagnosis of AD. Two cut points of p-tau217/Aβ42 were established in the Chinese population for clinical laboratory and community screening uses.
本研究旨在评估一种新型血浆磷酸化tau（p-tau）217/淀粉样β蛋白（Aβ）42比值检测对阿尔茨海默病（AD）的诊断性能。
在一个临床队列（n = 391）和一个社区队列（n = 121）中，以Aβ和tau正电子发射断层扫描（PET）作为参考标准，评估Lumipulse G血浆p-tau217/Aβ42比值的诊断性能。
血浆p-tau217/Aβ42在检测Aβ PET异常状态（曲线下面积[AUC]：0.963至0.966）和tau PET异常状态（AUC：0.947至0.974）方面表现出高性能，在临床和社区队列中，其性能在临床上等同于脑脊液（CSF）p-tau181/Aβ42和Aβ42/Aβ40，且高于血液p-tau217、Aβ42/Aβ40、p-tau181和p-tau181/Aβ42。采用双截断方法可提高特异性而不降低敏感性。在临床队列（10.6%对13.0%）和社区队列（16.5%对31.4%）中，p-tau217/Aβ42比值的中间百分比均低于单独的p-tau217。
血浆p-tau217/Aβ42在检测脑AD病理方面具有高性能，因此为AD的临床诊断和社区筛查提供了一种有前景的工具。
Lumipulse G血浆p-tau217和p-tau217/Aβ42比值在临床和社区队列中均准确识别了异常的Aβ和tau PET状态。血浆p-tau217和p-tau217/Aβ42比值的性能等同于脑脊液检测。在识别Aβ PET阳性方面，血浆p-tau217/Aβ42比值优于单独的p-tau217，且这种优势在社区队列中更明显，提示在AD早期诊断方面具有优势。在中国人群中建立了p-tau217/Aβ42的两个截断点，用于临床实验室和社区筛查。
