血浆生物标志物作为功能网络异常的核心介质：来自两项队列研究的证据。

Plasma biomarkers as core mediators in functional network abnormalities: Evidence from a two-cohort study.

作者信息

Wei Min, Zhang Ying, Wang Min, Zhong Jiayi, Chai Wenhui, Hu Wenjing, Tao Fengli, Wang Luyao, Zhang Qi, Yu Xianfeng, Shi Rong, Li Chenyang, Song Ziyan, Chen Guanqun, Zhang Shuyu, Jiang Jiehui, Han Ying

机构信息

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Institute of Biomedical Engineering, School of Medicine, Shanghai University, Shanghai, China.

出版信息

Alzheimers Dement. 2025 Apr;21(4):e70114. doi: 10.1002/alz.70114.

DOI:10.1002/alz.70114

PMID:40329658

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056302/

Abstract

INTRODUCTION

Researchers have reported an association among amyloid beta (Aβ), 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, Aβ 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, Aβ42/40) 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 Aβ stages, with differences mediated by plasma biomarkers. The crucial pathway exhibited fully mediated effects: Aβ 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 Aβ accumulation and in various functional network alterations.

HIGHLIGHTS

Plasma biomarkers demonstrated significant mediating effects on Aβ deposition and functional network alterations across different Aβ stages in both East Asian and Western cohorts. Significant functional connectivity variations in different brain networks were observed throughout AD progression in two cohorts, particularly across various Aβ stages. Among all plasma biomarkers, p-tau217 and p-tau181 demonstrated more comprehensive and fully mediating effects compared to other biomarkers, influencing connectivity alterations in the various functional networks. The plasma biomarkers exhibited great potential for tracking pathologic progression, functional network alterations, and early disease identification in East Asian and Western cohorts.

摘要

引言

研究人员报告了β-淀粉样蛋白（Aβ）、tau蛋白沉积和功能网络之间的关联。然而，血浆生物标志物是否介导这一过程仍不清楚。

方法

从两个独立队列SILCODE（n = 147）和ADNI（n = 201）中获取了348名有可用血浆生物标志物、Aβ正电子发射断层扫描（PET）和静息态功能磁共振成像的参与者。评估了血浆生物标志物、功能连接性和全局标准化摄取值比率（SUVR）之间的相关性，并分析了中介效应以探索潜在途径。

结果

血浆生物标志物（p-tau181、p-tau217、神经丝轻链、胶质纤维酸性蛋白、Aβ42/40）与全局SUVR和跨网络的功能连接性显著相关（p < 0.05）。在不同的Aβ阶段观察到不同网络中显著的功能连接性变化，这些差异由血浆生物标志物介导。关键途径表现出完全中介效应：Aβ PET SUVR - 血浆生物标志物（主要是p-tau181和p-tau217） - 各种功能网络。

讨论

我们的研究强调了血浆生物标志物（主要是p-tau181和p-tau217）在Aβ积累进展和各种功能网络改变中的核心中介作用。

要点

血浆生物标志物在东亚和西方队列的不同Aβ阶段对Aβ沉积和功能网络改变具有显著的中介作用。在两个队列的整个AD进展过程中，特别是在不同的Aβ阶段，观察到不同脑网络中显著的功能连接性变化。在所有血浆生物标志物中，与其他生物标志物相比，p-tau217和p-tau181表现出更全面和完全的中介作用，影响各种功能网络中的连接性改变。血浆生物标志物在追踪东亚和西方队列中的病理进展、功能网络改变和早期疾病识别方面具有巨大潜力。