在多中心、多种族老年人群中对用于检测和监测阿尔茨海默病的血浆tau生物标志物进行综合评估。

Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population.

作者信息

Lan Guoyu, Wang Mengjie, Gonzalez-Ortiz Fernando, Zhang Laihong, Li Anqi, Li Binyin, Jiang Mingxing, Yang Jie, Chen Xuhui, Shi Dai, Fan Xiang, Cai Yue, Sun Pan, Liu Lin, Li Jieyin, He Zhengbo, Fang Lili, Zhou Xin, Chen Linting, Wang Yiying, Li Mingxu, Liu Zhen, Wang Qingyong, Xu Linsen, Zhou Liemin, Cheng Guanxun, Wang Xinlu, Ran Pengcheng, Wang Lu, Sun Kun, Han Ying, Guan Yihui, Blennow Kaj, Xie Fang, Guo Tengfei

机构信息

Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.

Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Nat Aging. 2025 Jun 23. doi: 10.1038/s43587-025-00904-3.

DOI:10.1038/s43587-025-00904-3

PMID:40550877

Abstract

Over 20% of patients with Alzheimer's disease (AD) worldwide are Chinese, although the efficacy of existing blood-based measures of AD biomarkers is largely unknown in Asian cohorts. Here we explored how plasma tau biomarkers correlated with cross-sectional and longitudinal AD-related outcomes and their diagnostic performance in 1,085 participants from three independent studies, including two Chinese cohorts, Greater-Bay-Area Healthy Aging Brain Study (n = 425) and Huashan (n = 297), and the North American Alzheimer's Disease Neuroimaging Initiative cohort (n = 363). Plasma p-tau217 performed best in classifying Aβ-positron emission tomography (PET) and tau-PET positivity throughout the AD continuum and correlated with all AD-related outcomes. A two-cutoff approach suggested that participants with intermediate plasma p-tau217 levels experienced rapid accumulation of Aβ-PET and entorhinal tau-PET, as well as accelerated hypometabolism and cognitive decline. Increased plasma p-tau217 was also associated with rapid longitudinal changes in Aβ-PET, tau-PET and neurodegeneration. These results suggest that plasma p-tau217 is superior in detecting multiple aspects of AD-related pathological changes and tracking disease progression.

摘要

全球超过20%的阿尔茨海默病（AD）患者为中国人，尽管现有基于血液的AD生物标志物检测方法在亚洲人群中的有效性很大程度上未知。在此，我们在来自三项独立研究的1085名参与者中探讨了血浆tau生物标志物与横断面和纵向AD相关结局的相关性及其诊断性能，这三项研究包括两个中国队列，即大湾区健康老龄化脑研究（n = 425）和华山队列（n = 297），以及北美阿尔茨海默病神经影像学计划队列（n = 363）。在整个AD病程中，血浆p-tau217在区分Aβ正电子发射断层扫描（PET）和tau-PET阳性方面表现最佳，并且与所有AD相关结局相关。一种双临界值方法表明，血浆p-tau217水平处于中等的参与者经历了Aβ-PET和内嗅区tau-PET的快速积累，以及代谢减退和认知下降的加速。血浆p-tau217升高还与Aβ-PET、tau-PET和神经退行性变的快速纵向变化相关。这些结果表明，血浆p-tau217在检测AD相关病理变化的多个方面和追踪疾病进展方面具有优势。