血浆蛋白质组学分析可识别与阿尔茨海默病风险相关的蛋白质和信号通路。
Plasma proteomic analysis identifies proteins and pathways related to Alzheimer's risk.
作者信息
Huang Yen-Ning, Liu Shiwei, Park Tamina, Chaudhuri Soumilee, Kuchenbecker Lindsey A, Carrasquillo Minerva M, Ertekin-Taner Nilüfer, Bice Paula J, Zetterberg Henrik, Blennow Kaj, Russ Kristen, Dage Jeffrey L, Nudelman Kelly N H, Cruchaga Carlos, Brosch Jared R, Farlow Martin R, Clark David G, Mathew Sunu, Unverzagt Frederick, Gao Sujuan, Wang Sophia, Apostolova Liana G, Wilcock Donna M, Foroud Tatiana, Risacher Shannon L, Saykin Andrew J, Nho Kwangsik
机构信息
Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
出版信息
Alzheimers Dement. 2025 Aug;21(8):e70579. doi: 10.1002/alz.70579.
INTRODUCTION
We investigated associations of plasma proteins with blood-based amyloid/tau/neurodegeneration/inflammation (A/T/N/I) biomarkers for Alzheimer's disease (AD).
METHODS
Plasma proteomics and clinical data from the Indiana AD Research Center (N = 498) were used. Association analysis of plasma proteins with blood A/T/N/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort (N = 323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk.
RESULTS
We identified 35 proteins associated with AD, 20 of which were replicated in the independent cohort. We identified 150, 448, and 219 proteins associated with T/N/I biomarkers, respectively, revealing biomarker-specific pathways. Network analysis identified two modules associated with T/N/I biomarkers, preserved in cerebrospinal fluid (CSF), and their enriched pathways. The classification model of proteins effectively differentiated AD (area under the curve [AUC] = 0.930).
CONCLUSION
Our findings suggest dysregulated plasma proteins and pathways in AD, enhancing our understanding of molecular mechanisms and diagnostic strategies for AD.
HIGHLIGHTS
Plasma proteins were identified as being associated with Alzheimer's disease (AD) and plasma biomarkers. The identified proteins were replicated in both plasma and cerebrospinal fluid (CSF) proteomics. The identified proteins were associated with AD biomarker-specific pathways. The identified proteins improved the performance of the AD classification. Protein network analysis identified network modules and their enriched pathways.
引言
我们研究了血浆蛋白与阿尔茨海默病（AD）基于血液的淀粉样蛋白/ tau蛋白/神经退行性变/炎症（A/T/N/I）生物标志物之间的关联。
方法
使用了来自印第安纳州AD研究中心的血浆蛋白质组学和临床数据（N = 498）。对血浆蛋白与血液A/T/N/I生物标志物以及诊断进行了关联分析，随后在一个独立队列（N = 323）中进行复制、网络分析、通路富集和机器学习分类，以识别与AD风险相关的蛋白质和通路。
结果
我们鉴定出35种与AD相关的蛋白质，其中20种在独立队列中得到了验证。我们分别鉴定出150种、448种和219种与T/N/I生物标志物相关的蛋白质，揭示了生物标志物特异性通路。网络分析确定了两个与T/N/I生物标志物相关的模块，这些模块在脑脊液（CSF）中得以保留，以及它们富集的通路。蛋白质分类模型有效地鉴别了AD（曲线下面积[AUC]=0.930）。
结论
我们的研究结果表明AD患者血浆蛋白和通路失调，增进了我们对AD分子机制和诊断策略的理解。
重点
血浆蛋白被鉴定为与阿尔茨海默病（AD）和血浆生物标志物相关。所鉴定的蛋白质在血浆和脑脊液（CSF）蛋白质组学中均得到了验证。所鉴定的蛋白质与AD生物标志物特异性通路相关。所鉴定的蛋白质提高了AD分类的性能。蛋白质网络分析确定了网络模块及其富集的通路。
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