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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

脑脊液 生物标志物 医学 蛋白质组学 队列 蛋白质组 病理 疾病 神经退行性变 生物标志物发现 阿尔茨海默病 肿瘤科 内科学 生物信息学 生物 基因 生物化学
作者
Qing‐Qing Tao,Xue Cai,Yan‐Yan Xue,Weigang Ge,Liang Yue,Xiaoyan Li,Rong-Rong Lin,Guoping Peng,Wenhao Jiang,Sainan Li,Kun-Mu Zheng,Bin Jiang,Jianping Jia,Tiannan Guo,Zhi‐Ying Wu
出处
期刊:The Innovation [Elsevier BV]
卷期号:5 (1): 100544-100544 被引量:47
标识
DOI:10.1016/j.xinn.2023.100544
摘要

Amyloid-β, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.
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