INTRODUCTION: Researchers have reported an association among amyloid beta (A beta), tau deposition, and functional networks. Nevertheless, whether plasma biomarkers mediate this process remains unclear. METHODS: Three hundred and forty-eight participants with available plasma biomarkers, A beta positron emission tomography (PET), and resting-state functional magnetic resonance imaging were obtained from two independent cohorts: SILCODE (n = 147) and ADNI (n = 201). Correlations among plasma biomarkers, functional connectivity, and global standardized uptake value ratio (SUVR) were assessed, and mediating effects were analyzed to explore underlying pathways. RESULTS: Plasma biomarkers (p-tau181, p-tau217, neurofilament light, glial fibrillary acidic protein, A beta 42/40) demonstrated significant correlations with global SUVR and functional connectivity across networks (p < 0.05). Significant functional connectivity variations in different networks were observed across various A beta stages, with differences mediated by plasma biomarkers. The crucial pathway exhibited fully mediated effects: A beta PET SUVR-plasma biomarkers (mainly p-tau181 and p-tau217) - various functional networks. DISCUSSION: Our study highlights the core mediating role of plasma biomarkers (mainly p-tau181 and p-tau217) in the progression of A beta accumulation and in various functional network alterations.
基金：
National Natural Science Foundation of China [U01 AG024904]; ADNI (National Institutes of Health) [W81XWH-12-2-0012]; DOD ADNI (Department of Defense); National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; Biogen; CereSpir, Inc.; Cogstate; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; Fujirebio; Johnson & Johnson Pharmaceutical Research & Development LLC.; Merck Co., Inc.; Meso Scale Diagnostics; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; ADNI clinical sites in Canada; Foundation for the National Institutes of Health; Northern California Institute for Research and Education [82020108013, 82327809, 2022ZD0211800, M-0759]; Laboratory for Neuro Imaging at the University of Southern California - National Natural Science Foundation of China; Shenzhen Bay Scholars Program
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China[5]Cent Hosp Karamay, Karamay, Xinjiang, Peoples R China[8]Hainan Univ, Sch Biomed Engn, State Key Lab Digital Med Engn, Key Lab Biomed Engn Hainan Prov, Sanya, Peoples R China[9]Shenzhen Bay Lab, Inst Biomed Engn, Shenzhen, Peoples R China[10]Natl Clin Res Ctr Geriatr Dis, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Wei Min,Zhang Ying,Wang Min,et al.Plasma biomarkers as core mediators in functional network abnormalities: Evidence from a two-cohort study[J].ALZHEIMERS & DEMENTIA.2025,21(4):doi:10.1002/alz.70114.
APA：
Wei, Min,Zhang, Ying,Wang, Min,Zhong, Jiayi,Chai, Wenhui...&Han, Ying.(2025).Plasma biomarkers as core mediators in functional network abnormalities: Evidence from a two-cohort study.ALZHEIMERS & DEMENTIA,21,(4)
MLA：
Wei, Min,et al."Plasma biomarkers as core mediators in functional network abnormalities: Evidence from a two-cohort study".ALZHEIMERS & DEMENTIA 21..4(2025)
医学