To investigate the mechanism of TREM2/DAP12 complex in mediating inflammatory responses that affect β-amyloid plaque deposition in Alzheimer's disease (AD) modeled mice. We measured escape latency and platform crossing time using the Morris water maze image automatic acquisition and software analysis system in TREM2 and DAP12 microglia knockout AD model mouse. We monitored the deposition of Aβ plaques in the mouse hippocampus using Congo red staining and measured levels. of inflammatory factors IL-6 and TNF-α by ELISA. Newborn mice with TREM2 knockout were selected for primary microglia isolation and culture, and Aged oligomer Aβ1-42 was added to the microglial culture medium to simulate the AD environment in vivo. Co-immunoprecipitation assay was used to detect the interaction between DAP12 and TREM2, and measured the inflammatory response induced by lipopolysaccharide (LPS) in mice with TREM2 and DAP12 knockdown through adeno-associated virus in BV2 microglia. The escape latency of the AD model mice with TREM2 and DAP12 knockout was higher and the number of crossing platforms lower than in the control group, whereas Aβ deposition and levels of inflammatory factors were higher. In TREM2 knockout microglial cultured with Aβ1-42, levels of IL-6 and TNF-α increased. Immunoprecipation pull-down assays showed that TREM2 binds to the membrane receptor DAP12 to form a complex. Knockout of TREM2 or DAP12 can inhibit LPS-induced microglial inflammatory responses. The TREM2/DAP12 complex inhibits the microglial inflammatory response through the JNK signaling pathway, thereby reducing the deposition of Aβ plaques and attenuation the behavioral manifestation in a mouse AD model.

研究 TREM2/DAP12 复合物在介导影响阿尔茨海默病 (AD) 模型小鼠 β-淀粉样蛋白斑块沉积的炎症反应中的机制。我们在 TREM2 和 DAP12 小胶质细胞敲除 AD 模型小鼠中使用 Morris 水迷宫图像自动采集和软件分析系统测量了逃逸潜伏期和平台穿越时间。我们使用刚果红染色和测量水平监测了小鼠海马中 Aβ 斑块的沉积。ELISA法检测炎症因子IL-6和TNF-α。选择具有TREM2敲除新生小鼠初级小胶质细胞分离和培养，以及老年人低聚物Aβ1-42加入到小神经胶质培养介质来模拟AD环境体内. 采用免疫共沉淀法检测 DAP12 和 TREM2 之间的相互作用，并通过 BV2 小胶质细胞中的腺相关病毒测量了 TREM2 和 DAP12 敲低小鼠的脂多糖（LPS）诱导的炎症反应。与对照组相比，TREM2和DAP12基因敲除的AD模型小鼠的逃逸潜伏期较高，交叉平台数较少，而Aβ沉积和炎症因子水平较高。在用 Aβ1-42 培养的 TREM2 敲除小胶质细胞中，IL-6 和 TNF-α 的水平增加。免疫沉淀下拉分析表明 TREM2 与膜受体 DAP12 结合形成复合物。敲除 TREM2 或 DAP12 可以抑制 LPS 诱导的小胶质细胞炎症反应。