The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Department of Neurology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Cells. 2022 Aug 1;11(15):2365. doi: 10.3390/cells11152365.
Many studies have demonstrated that neuroinflammation contributes to the onset and development of Alzheimer's disease (AD). The infiltration of immune cells in the brain was observed in AD. The purpose of the present study was to verify potential mechanisms and screen out biomarkers related to immune infiltration in AD. We collected the expression profiling datasets of AD patients and healthy donors from the NCBI's Gene Expression Omnibus (GEO) database. We confirmed that immune-related mechanisms were involved in AD using differentially expressed genes analysis and functional enrichment analysis. We then found that M2 macrophage infiltration was most positively correlated with AD according to the CIBERSORT algorithm and a weighted gene co-expression network analysis (WGCNA). , , , and were identified as hub genes correlated with M2 macrophage infiltration in AD. Furthermore, the expression levels of these hub genes were positively correlated with Aβ42 and β-secretase activity. A diagnostic model of these hub genes was constructed, which showed a high area under the curve (AUC) value in both the derivation and validation cohorts. Overall, our work further expanded our understanding of the immunological mechanisms of AD and provided new insights into therapeutic strategies in AD.
许多研究表明神经炎症有助于阿尔茨海默病（AD）的发病和发展。在 AD 中观察到免疫细胞浸润到大脑中。本研究的目的是验证潜在的机制并筛选出与 AD 免疫浸润相关的生物标志物。我们从 NCBI 的基因表达综合数据库（GEO）中收集了 AD 患者和健康供体的表达谱数据集。我们使用差异表达基因分析和功能富集分析证实了 AD 中涉及免疫相关机制。然后，我们根据 CIBERSORT 算法和加权基因共表达网络分析（WGCNA）发现，M2 巨噬细胞浸润与 AD 最正相关。,,, 和 被鉴定为与 AD 中 M2 巨噬细胞浸润相关的枢纽基因。此外，这些枢纽基因的表达水平与 Aβ42 和 β-分泌酶活性呈正相关。构建了这些枢纽基因的诊断模型，在推导和验证队列中均表现出较高的曲线下面积（AUC）值。总的来说，我们的工作进一步扩展了我们对 AD 免疫机制的理解，并为 AD 的治疗策略提供了新的见解。
