随着人口老龄化，阿尔茨海默病（AD）成为全球主要负担疾病之一。本研究旨在通过生物信息学分析探讨快速加速纤维肉瘤-1（RAF-1）在AD中的潜在分子机制。在GSE132903数据集中进行差异基因表达分析。我们使用权重基因相关网络分析（WGCNA）来评估共表达模块之间的关系并构建全局调控网络。通过功能富集分析鉴定了 RAF-1 在 AD 中的串扰通路。总共，在 AD 与非痴呆对照以及 RAF-1 高组与低组之间选择了 2700 个差异表达基因 (DEG)。其中，turquoise模块中与AD强相关且RAF-1高表达的DEG富集于血管内皮生长因子（VEGF）、神经营养素、丝裂原激活蛋白激酶（MAPK）信号通路、氧化磷酸化、GABA能突触和轴突指导。此外，全球监管网络还确定了 RAF-1 的串扰通路，包括 MAPK、VEGF、神经营养蛋白信号通路和轴突引导。 AUC的性能评价为84.2%。基因集富集分析（GSEA）表明氧化磷酸化和突触相关的生物过程在RAF-1-high和AD组中富集。我们的研究结果强化了高 RAF-1 水平在 AD 发病机制中的潜在作用，该发病机制由 MAPK、VEGF、神经营养蛋白信号通路和轴突引导介导。© 2023。作者获得 Springer Science Business Media 的独家许可， LLC，施普林格自然集团的一部分。

Alzheimer's disease (AD) becomes one of the main global burden diseases with the aging population. This study was to investigate the potential molecular mechanisms of rapidly accelerated fibrosarcoma-1 (RAF-1) in AD through bioinformatics analysis. Differential gene expression analysis was performed in GSE132903 dataset. We used weight gene correlation network analysis (WGCNA) to evaluate the relations among co-expression modules and construct global regulatory network. Cross-talking pathways of RAF-1 in AD were identified by functional enrichment analysis. Totally, 2700 differentially expressed genes (DEGs) were selected between AD versus non-dementia control and RAF-1-high versus low group. Among them, DEGs in turquoise module strongly associated with AD and high expression of RAF-1 were enriched in vascular endothelial growth factor (VEGF), neurotrophin, mitogen-activated protein kinase (MAPK) signaling pathway, oxidative phosphorylation, GABAergic synapse, and axon guidance. Moreover, cross-talking pathways of RAF-1, including MAPK, VEGF, neurotrophin signaling pathways, and axon guidance, were identified by global regulatory network. The performance evaluation of AUC was 84.2%. The gene set enrichment analysis (GSEA) indicated that oxidative phosphorylation and synapse-related biological processes were enriched in RAF-1-high and AD group. Our findings strengthened the potential roles of high RAF-1 level in AD pathogenesis, which were mediated by MAPK, VEGF, neurotrophin signaling pathways, and axon guidance.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.