Chen Jiongxue, Xie Jiatian, Deng Fuyin, Cai Jinhua, Chen Sitai, Song Xingrong, Xia Shangzhou, Shen Qingyu, Guo Xinying, Tang Yamei
Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Department of Anesthesiology, Guangzhou Women and Children Medical Center, Guangzhou 510623, China.
Genomics. 2025 Jan;117(1):110976. doi: 10.1016/j.ygeno.2024.110976. Epub 2024 Dec 8.
The significance of the adaptive immune response in Alzheimer's disease (AD) is increasingly recognized. We analyzed scRNA-Seq data from AD patients, revealing a notable rise in CD4 cytotoxic T cells (CD4-CTLs) in peripheral blood mononuclear cells (PBMCs), validated in vivo and in vitro. This rise correlates with cognitive decline in AD patients. We also identified transcription factors TBX21 and MYBL1 as key drivers of CD4-CTL expansion. Further analyses indicate these cells are terminally differentiated, showing clonal expansion, metabolic changes, and unique communication patterns. Mendelian randomization identified risk genes SRGN and ITGB1, suggesting their genetic regulation in CD4-CTLs may contribute to AD. To summarize, our findings characterize the expansion of CD4-CTLs in the PBMCs of AD patients, providing valuable understanding into the possible mechanisms involved in the expansion of CD4-CTLs in AD.
适应性免疫反应在阿尔茨海默病（AD）中的重要性日益得到认可。我们分析了AD患者的单细胞RNA测序（scRNA-Seq）数据，发现外周血单核细胞（PBMC）中CD4细胞毒性T细胞（CD4-CTLs）显著增加，并在体内和体外得到验证。这种增加与AD患者的认知衰退相关。我们还确定转录因子TBX21和MYBL1是CD4-CTLs扩增的关键驱动因素。进一步分析表明，这些细胞是终末分化的，表现出克隆性扩增、代谢变化和独特的通讯模式。孟德尔随机化确定了风险基因SRGN和ITGB1，表明它们在CD4-CTLs中的遗传调控可能与AD有关。总之，我们的研究结果描述了AD患者PBMC中CD4-CTLs的扩增情况，为了解AD中CD4-CTLs扩增的可能机制提供了有价值的见解。
