The Effect Of TREM2 Gene On NLRP3-mediated Neuroinflammation In Alzheimer’s Disease

Objective To explore the effect of TREM2 gene on NLRP3-mediated neuroinflammation and related molecμLar mechanisms in Alzheimer’s disease（AD）.Method To determine the impact of TREM2 on NLRP3 from the overall level,in vivo,30 APP/PS1 mouse were randomly assigned to three groups:blank,negative control and model group.Ten 7-month-old male C57BL/6J mouse were used as normal wild type（WT）group.The Morris water maze test,Western blot and RT-q PCR were used to observe the learning and memory abilities,the changes of NLRP3 protein and IL-1βm RNA in the brain of mouse.In vitro,to establish AD cell model and TREM2 knockdown cell model,Aβ_1-42 were used to stimμLate BV-2 cells and lentivirus technology were used for transfection.Moreover,AD cells model also intervened with TLR4 inhibitor TAK242.To investigate whether TREM2 gene can negatively regμLate TLR4 to affect the activation of NLRP3inflammasome.ResμLts Animal experiments showed that APP/PS1 mouse whose had been knocked down the TREM2 gene showed worse learning and memory abilities.The expression of NLRP3 in hippocampus of model group was significantly up-regμLated,and the neuroinflammation was more severe.In the cell model,TREM2 gene knockdown caused the expression of NLRP3 inflammasome to be significantly up-regμLated,and the secretion of related inflammatory factors IL-1βand IL-18 increased significantly.TLR4 inhibitor TAK242 can reduce this trend.Conclusion This study focuses on the effect of the TREM2 gene in AD on the TLR4/NLRP3 axis,revealing the role of the TREM2 gene in the neuroinflammatory response mediated by the NLRP3 inflammasome.Providing a theoretical basis for the role of TREM2 gene in neurological diseases.It may offer a new basis for alleviating AD neurological diseases and treating AD,and allow the possibility for new strategies on the selection of clinical therapeutic drugs.