目的 利用生物信息學(xué)技術(shù)篩選阿爾茨海默?。ˋD）不同腦區(qū)差異表達(dá)基因，探討各腦區(qū)的免疫機(jī)制，以預(yù)測(cè)潛在的治療中藥。方法 從 GEO數(shù)據(jù)庫(kù)獲得 AD的樣本數(shù)據(jù)，進(jìn)行差異表達(dá)基因（DEGs）分析及加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析（WGCNA），對(duì)各腦區(qū)最相關(guān)的模塊進(jìn)行蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析獲得核心基因，并使用受試者工作特征曲線（ROC）曲線評(píng)估其診斷價(jià)值。對(duì)差異基因進(jìn)行免疫通路富集分析，并使用 CIBERSORT算法分析免疫細(xì)胞浸潤(rùn)模式，通過 Coremine Medical篩選治療 AD的潛在中藥。結(jié)果 大腦的內(nèi)嗅皮層（EC）區(qū)有 3 280個(gè)差異基因、海馬體（HIP）區(qū)有 1 591個(gè)差異基因、內(nèi)側(cè)顳回（MTG）區(qū)有 3 995個(gè)差異基因、后扣帶（PC）區(qū)有 2 056個(gè)差異基因、額上回（SFG）區(qū)有907個(gè)差異基因、初級(jí)視覺皮層（VCX）區(qū)有1 480個(gè)差異基。其中EC與VCX區(qū)與blue模塊相關(guān)性高、HIP與PC區(qū)與turquoise模塊相關(guān)性高、MTG、SFG別與綠色和黃色模塊相關(guān)性高。PPI網(wǎng)絡(luò)顯示 EC區(qū)有 4個(gè) Hub基因，HIP區(qū)有 13個(gè)Hub基因，MTG區(qū)有 4個(gè) Hub基因，PC區(qū)有 9個(gè) Hub基因，SFG區(qū)有 17個(gè) Hub基因，VCX區(qū)有 13個(gè) Hub基因。不同腦區(qū)富集有不同免疫通路的模塊。通過基因映射到姜黃為治療 AD的潛在中藥，其映射到 EP300、PPARG、CCND1、GSK3B、BCL2、EGFR、KDR、MYC和IL1B等基因上。結(jié)論 AD患者在不同腦區(qū)表現(xiàn)出多樣化的免疫途徑，這種差異與AD發(fā)病機(jī)制緊密相連。姜黃有望作為治療AD的潛在中藥。

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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山西省科技創(chuàng)新人才團(tuán)隊(duì)項(xiàng)目（202204051002032）；山西省中醫(yī)藥管理局資助項(xiàng)目（2023ZYYC2034）；山西省衛(wèi)健委衛(wèi)生健康科研課題（2021031）