目的 利用生物信息学技术筛选阿尔茨海默病（AD）不同脑区差异表达基因，探讨各脑区的免疫机制，以预测潜在的治疗中药。方法 从 GEO数据库获得 AD的样本数据，进行差异表达基因（DEGs）分析及加权基因共表达网络分析（WGCNA），对各脑区最相关的模块进行蛋白质-蛋白质相互作用（PPI）网络分析获得核心基因，并使用受试者工作特征曲线（ROC）曲线评估其诊断价值。对差异基因进行免疫通路富集分析，并使用 CIBERSORT算法分析免疫细胞浸润模式，通过 Coremine Medical筛选治疗 AD的潜在中药。结果 大脑的内嗅皮层（EC）区有 3 280个差异基因、海马体（HIP）区有 1 591个差异基因、内侧颞回（MTG）区有 3 995个差异基因、后扣带（PC）区有 2 056个差异基因、额上回（SFG）区有907个差异基因、初级视觉皮层（VCX）区有1 480个差异基。其中EC与VCX区与blue模块相关性高、HIP与PC区与turquoise模块相关性高、MTG、SFG别与绿色和黄色模块相关性高。PPI网络显示 EC区有 4个 Hub基因，HIP区有 13个Hub基因，MTG区有 4个 Hub基因，PC区有 9个 Hub基因，SFG区有 17个 Hub基因，VCX区有 13个 Hub基因。不同脑区富集有不同免疫通路的模块。通过基因映射到姜黄为治疗 AD的潜在中药，其映射到 EP300、PPARG、CCND1、GSK3B、BCL2、EGFR、KDR、MYC和IL1B等基因上。结论 AD患者在不同脑区表现出多样化的免疫途径，这种差异与AD发病机制紧密相连。姜黄有望作为治疗AD的潜在中药。

Objective To identify differentially expressed genes (DEGs) in different brain regions of Alzheimer's disease (AD) using bioinformatics techniques, explore the immune mechanisms in each brain region, and predict potential therapeutic drugs.Methods AD sample data were obtained from the GEO database, and DEGs analysis and weighted gene co-expression network analysis (WGCNA) were performed on each brain region. The core genes in the most related modules were obtained by protein-protein interaction (PPI) network analysis, and their diagnostic value was evaluated by ROC curve. Differential genes were subjected to immune pathway enrichment analysis, and immune cell infiltration patterns were analyzed using CIBERSORT algorithm. Potential therapeutic drugs for AD were screened using Coremine Medical.Results A total of 3 280 differential genes were identified in the EC region, 1 591 in the HIP region, 3 995 in the MTG region, 2 056 in the PC region, 907 in the SFG region, and 1 480 in the VCX region. EC and VCX were highly related to the blue module, HIP and PC were highly related to the turquoise module, and MTG and SFG were highly related to the green and yellow modules. The PPI network showed that there were four Hub genes in the EC region, 13 in the HIP region, four in the MTG region, nine in the PC region, and 17 in the SFG region. Different brain regions were enriched with different immune pathway modules. Subsequently, Curcumae Longae Rhizoma was identified as a potential traditional Chinese medicine (TCM) for AD treatment based on its association with key genes such as EP300, PPARG, CND1, GSK3B, BCL2, EGFR, KDR, MYC, and IL1B.Conclusion AD patients exhibit diverse immune pathways across distinct brain regions, and this disparity is intricately associated with the pathogenesis of AD. Curcumae Longae Rhizoma holds promising potential as a Chinese medicinal intervention for the treatment of AD.

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山西省科技创新人才团队项目（202204051002032）；山西省中医药管理局资助项目（2023ZYYC2034）；山西省卫健委卫生健康科研课题（2021031）