Liu Yaqiong, Li Tao, Xiong Juliang
Regenerative Medicine Institute (REMEDI), Biomedical Sciences Building, University of Galway, Galway, Ireland.
Department of Pharmacy, the Second Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, China.
Metab Brain Dis. 2025 Jan 4;40(1):85. doi: 10.1007/s11011-024-01516-3.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and the aggregation of tau protein, resulting in intense memory loss and dementia. Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus, which is associated with decreased cognitive function and impaired memory. A growing body of literature emphasize the involvement of microglia in AD and DACD. Although AD and DACD share some common features related to symptomatology and pathophysiology, the characteristics and heterogeneity of microglia remain largely unknown in these two diseases. In this study, multiple bioinformatics analyses were performed to analyze the frequency, altered genes, cell-cell communication, and subtypes of microglia in AD and DACD mouse models based on two publicly single-nucleus RNA sequencing (snRNA-Seq) datasets. The results revealed that the frequency of microglia was increased in both AD and DACD mouse models when compared with control mice. After analyzing the differentially expressed genes of microglia from the two mouse models, only six common upregulated genes were found. The CellChat analysis revealed the complex cell-cell communication network (microglia clusters with other cell types) in 5XFAD vs. control mice and db/db vs. control mice. The microglia subtypes and their transcription factor activity profile in 5XFAD mice were different from that in db/db mice. In summary, this study provided some insights into the alterations of microglia in 5XFAD and db/db mice, which might open up potential avenues for the microglial-targeted therapy in AD and DACD.
阿尔茨海默病（AD）的特征是β淀粉样蛋白（Aβ）斑块的积累和tau蛋白的聚集，导致严重的记忆丧失和痴呆。糖尿病相关认知功能障碍（DACD）是糖尿病的一种并发症，与认知功能下降和记忆受损有关。越来越多的文献强调小胶质细胞在AD和DACD中的作用。尽管AD和DACD在症状学和病理生理学方面有一些共同特征，但在这两种疾病中，小胶质细胞的特征和异质性在很大程度上仍然未知。在本研究中，基于两个公开的单核RNA测序（snRNA-Seq）数据集，进行了多项生物信息学分析，以分析AD和DACD小鼠模型中小胶质细胞的频率、基因改变、细胞间通讯和亚型。结果显示，与对照小鼠相比，AD和DACD小鼠模型中小胶质细胞的频率均增加。在分析了来自两种小鼠模型的小胶质细胞差异表达基因后，仅发现六个共同上调的基因。CellChat分析揭示了5XFAD与对照小鼠以及db/db与对照小鼠之间复杂的细胞间通讯网络（小胶质细胞簇与其他细胞类型）。5XFAD小鼠中的小胶质细胞亚型及其转录因子活性谱与db/db小鼠不同。总之，本研究为5XFAD和db/db小鼠中小胶质细胞的改变提供了一些见解，这可能为AD和DACD的小胶质细胞靶向治疗开辟潜在途径。
