Development of a Plasma Biomarker Diagnostic Model Incorporating Ultrasensitive Digital Immunoassay as a Screening Strategy for Alzheimer Disease in a Chinese Population

Author:

Wu Xue1,Xiao Zhenxu23,Yi Jingwei1,Ding Saineng23,Gu Hongchen1,Wu Wanqing23,Luo Jianfeng45,Liang Xiaoniu23,Zheng Li23,Xu Hong1ORCID,Zhao Qianhua236,Ding Ding23

Affiliation:

1. School of Biomedical Engineering/Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China

2. Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China

3. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China

4. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China

5. Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China

6. MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China

Abstract

Abstract Background The ultrasensitive detection of blood-based biomarkers such as amyloid β (Aβ), tau, and neurofilament light (NFL) has drawn much attention in Alzheimer disease (AD) diagnosis. However, few studies have been conducted in the Chinese population. This study aimed to evaluate the ability of plasma biomarker diagnostic models for AD in the Chinese population based on a novel digital immunoassay technology. Methods 159 patients with AD, 148 patients with amnestic mild cognitive impairment (aMCI), and 121 cognitively normal control participants were recruited from 2 cohorts. The concentrations of plasma Aβ42, Aβ40, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau 181), and NFL were quantified using an ultrasensitive single molecule array (Simoa) platform. Comprehensive and simplified diagnostic models were established based on the plasma biomarker profile and clinical characteristics. Results Among all blood biomarkers, p-tau181 had the greatest potential for identifying patients with cognitive impairment. The simplified diagnostic model, which combined plasma p-tau181, Aβ42, and clinical features, achieved 93.3% area under the curve (AUC), 78.6% sensitivity, and 94.2% specificity for distinguishing AD from control participants, indicating a diagnostic ability approaching that of the comprehensive diagnostic model including 5 plasma biomarkers and clinical characteristics (95.1% AUC, 85.5% sensitivity, 94.2% specificity). Moreover, the simplified model reached 95.9% AUC and 94.0% AUC for early- and late-onset AD/control participants, respectively. Conclusions We established AD diagnostic models using plasma biomarkers for Chinese participants. These findings suggest the simplified diagnostic model provides an accessible and practical way for large-scale screening in the clinic and community, especially in developing countries.

Funder

Shanghai Zhangjiang National Innovation Demonstration Zone

Shanghai Hospital Development Center

MOE Frontiers Center for Brain Science

Scientific Research Plan Project of Shanghai Science and Technology Committee

National Project of Chronic Disease

National Natural Science Foundation of China

Shanghai Municipal Science and Technology Major Project

Shanghai Sailing Program

ZJLab

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

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