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Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages

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资源类型：
Pubmed体系：
作者：
Wang Zhibo[1] * ; Chen Yuhan[2] ; Gong Katherine[3,4] ; Zhao Bote[1] ; Ning Yuye[1] ; Chen Meilin[1] ; Li Yan[1] ; Ali Muhammad[3,4] ; Timsina Jigyasha[3,4] ; Liu Menghan[3,4] ; Cruchaga Carlos[3,4,5,6,7] ; Jia Jianping[1,8,9,10,11] ;
机构： [1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, P.R.China [2]The First Clinical Medical School, Hebei North University, Zhangjiakou 075000, China [3]Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA [4]NeuroGenomics and Informatics Center, Washington University, St. Louis, MO, USA [5]Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA [6]Hope Center for Neurologic Diseases, Washington University, St. Louis, MO, USA [7]Knight Alzheimer’s Disease Research Center, Washington University, St. Louis, MO, USA [8]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing 100053, P.R.China [9]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing 100053, P.R.China [10]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100053, P.R.China [11]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, P.R.China
出处：
DOI： 10.1016/j.xcrm.2025.102031

摘要：
Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as HCLS1-associated protein X-1 (HAX1) and glucose-6-phosphate isomerase (GPI), that differentiated A+T+ from A+T- stages. These signatures outperform the established CSF biomarkers (area under the curve [AUC]: 0.92 versus 0.67-0.70) and accurately predicted disease progression over a decade. The findings are validated in both internal and external cohorts. These results underscore the potential of proteomic-based signatures to refine AD diagnostic criteria and improve patient stratification in clinical trials.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
CSF Somalogic (7K) and Metabolomics (Metabolon HD4) data generation and QC was supported by grants from the National Institutes of Health (RF1AG074007 [PI: Yun Ju Sung], R01AG044546 [PI: C.C.], P01AG003991 [PI: John Morris and C.C.], RF1AG053303 [PI: C.C.], RF1AG058501 [PI: C.C.], and U01AG058922 [PI: C.C.]), the Chan Zuckerberg Initiative (CZI), and the Alzheimer’s Association Zenith Fellows Award (ZEN22-848604, awarded to C.C.). The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444 (PI: John Morris and C.C.), P01AG03991 (PI: John Morris and C.C.), and P01AG026276 (PI: John Morris and C.C.). This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https:// neurogenomics.wustl.edu/), and the Departments of Neurology and Psychiatry at Washington University School of Medicine.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 2 区 细胞生物学
第一作者：
第一作者机构： [1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, P.R.China
通讯作者：
通讯机构： [1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing 100053, P.R.China [3]Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA [4]NeuroGenomics and Informatics Center, Washington University, St. Louis, MO, USA [5]Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA [6]Hope Center for Neurologic Diseases, Washington University, St. Louis, MO, USA [7]Knight Alzheimer’s Disease Research Center, Washington University, St. Louis, MO, USA [8]Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing 100053, P.R.China [9]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing 100053, P.R.China [10]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing 100053, P.R.China [11]Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing 100053, P.R.China
推荐引用方式(GB/T 7714)：
Wang Zhibo,Chen Yuhan,Gong Katherine,et al.Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages[J].Cell Reports. Medicine.2025,102031.doi:10.1016/j.xcrm.2025.102031.
APA：
Wang Zhibo,Chen Yuhan,Gong Katherine,Zhao Bote,Ning Yuye...&Jia Jianping.(2025).Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages.Cell Reports. Medicine,,
MLA：
Wang Zhibo,et al."Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages".Cell Reports. Medicine .(2025):102031

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