Mechanism Of TREM2 Gene Mediating Inflammation Regulation In Late-onset AD(LOAD)

Background: Late onset Alzheimer’s disease(load)is an important subtype of Alzheimer’s disease(AD).The core and basis of its pathogenesis are the abnormal accumulation of extracellular β-amyloid protein(Aβ)and the neurotoxic effect caused by it.Studies have shown that the myeloid cell trigger receptor-2(TREM2)gene is related to the pathogenesis of load,which plays an important role in mediating microglial phagocytosis of Aβ protein and regulating central neuritis.However,the exact mechanism is not clear.Objective: To investigate the regulatory effect of TREM2 on Aβ1-42-mediated neuroinflammation and its mechanism.Methods: Aβ1-42 was used to establish a classical ad cell model,and the TREM2 gene in BV-2 cells(microglia)was knockout and overexpressed by lentivirus.CCK8 method was used to detect the effect of TREM2 gene on the activity of AD cells;flow cytometry and enzyme linked immunosorbent assay were used to detect the transfection efficiency of lentivirus and the expression level of TREM2 gene;RT-PCR and ELISA were used to detect the level of inflammatory mediators(IL-1 β,IL-6 and TNF-a);western blot was used The protein levels of TLR2,TLR4 and TLR6 were detected by blot and immunofluorescence.The cells were treated with LPS,the activator of TLR,and the expression level of inflammatory factor protein was detected by WB.Results: Overexpression of TREM2 can significantly reverse the decreased activity of BV-2 cells caused by Aβ1-42,and reduce the secretion of Aβ1-42-mediated inflammatory mediators in BV-2 cells;more importantly,the expression of TLR2,TLR4 and TLR6 in Alzheimer’s disease microenvironment is significantly increased,and overexpression of TREM2 can down regulate the levels of TLR2,TLR4 and TLR6 in BV-2 cells.In addition,TLRs receptor agonist LPS treatment of BV-2,over expression of TREM2 mediated anti-inflammatory effect was significantly reversed,down-regulation of inflammatory factors was weakened.Conclusion: TREM2 can improve neuroinflammation mediated by Aβ1-42 in BV-2 cells,and its anti-inflammatory effect on ad is achieved by inhibiting TLR signal pathway.