这篇文章介绍了一项通过整合大规模蛋白质组学和遗传数据而开发的多尺度蛋白质组学网络模型，旨在揭示阿尔茨海默病（AD）的发病机制。研究人员分析了易受AD影响的脑区，如海马旁回（PHG）的蛋白质组，识别出数百个与AD相关的蛋白质共表达模块，其中一个关键模块揭示了神经元与胶质细胞（如星形胶质细胞和小胶质细胞）之间的相互作用失调。通过贝叶斯因果网络分析，研究确定了如AHNAK等关键驱动蛋白（KDPs），并通过人诱导多能干细胞（iPSC）模型进行实验验证。实验结果显示，下调星形胶质细胞驱动蛋白AHNAK可减少pTau和Aβ水平，并改善神经元活动，从而证实了这些KDPs是潜在的AD治疗靶点。References: Wang E, Yu K, Cao J, et al. Multiscale proteomic modeling reveals protein networks driving Alzheimer’s disease pathogenesis[J]. Cell, 2025.
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