ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Validation of the Robustness of Blood-based Biomarkers for Predicting Amyloid-β Positivity in Chinese Populations
Provisionally accepted
- 1Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
- 2Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China
- 3Huashan Hospital Fudan University PET Center, Shanghai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Blood-based biomarkers (BBBs) of Alzheimer's disease (AD) provide a promising, minimally invasive alternative for detecting cerebral amyloid-β (Aβ) pathology. However, a lack of robust validation across diverse platforms and populations has hindered their broader clinical adoption. Objective: This study aimed to cross-platform validation of the robustness of BBBs for predicting Aβ positivity in a Chinese population. Methods: The whole cohort (N=1,254) of AD clinical spectrum underwent cognitive assessments, cranial MRI scans, and Aβ PET scans. Sub-cohort 1 (N=504) underwent Simoa-based quantification of peripheral blood Aβ40, Aβ42, p-tau181, and NfL. Subcohort 2 (N=262) underwent additional single molecule assays (Simoa) based quantification of p-tau217 and GFAP. The whole cohorts (Subcohort 1, Subcohort 2, and the remaining population) were measured for the aforementioned six biomarkers (Aβ40, Aβ42, p-tau181, p-tau217, NfL, and GFAP) using light-initiated chemiluminescent assays (LiCA). We validated the robustness of BBBs for predicting Aβ positivity in Chinese populations, with a focus on p-tau217. Results: The BBBs of Aβ42/40, p-tau181, p-tau217, GFAP, and NfL have demonstrated remarkable robustness in identifying Aβ positivity within the Chinese population, as evidenced by both LiCA and Simoa assays. Among these markers, p-tau217 has emerged as the most accurate, performing robustness in both the whole cohort and cognitively normal individuals. Utilizing a dual-threshold approach for p-tau217, only 16% of samples fell into the intermediate range, thus requiring additional Aβ PET testing. Conclusions: BBBs have demonstrated good robustness for predicting Aβ pathology in the Chinese population, with plasma p-tau217 standing out as the most promising marker for early detection of AD-related changes.
Keywords: Alzheimer's disease, blood-based biomarkers, amyloid-β, p-tau217, biomarker robustness
Received: 06 Jul 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Wang, Cui, Pan, Zhang, Huang, Miao, Guan and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qihao Guo, qhguo@sjtu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.