Objective To establish a cell model of Alzheimer's disease(AD)in HT22 cells induced by Aβ1-42,and explore the targeted signaling pathway of Aβ-induced neuronal injury and cell apoptosis in this model.Methods HT22 cells were treated with different concentrations of Aβ 1-42(0,0.625,1.25,2.5,5,10,20,40 μmol/L)to screen the optimal concentration for AD cell model.Sub-sequently,the cell morphology was observed and the cell viability was detected at 6,12,24,48 h after the intervention of the optimal concentration to screen the optimal time for AD cell model.HT22 cells in the logarithmic phase of growth were intervened with 20 μmol/L Aβ1-42+PBS and PBS for 24 h for subsequent experiments in AD group and NC group,respectively.The expressions of apoptosis indicator(cleaved-Caspase-3),neurotrophic factor(NRN1),and synaptic indicators(SYP,MAP-2)were detected by Western blot.The expression and distribution of MAP-2 was detected by immunofluorescence.The AD-related signaling pathway was predicted by bioinformatics,and the phosphorylation level of ERK signaling pathway was verified by Western blot.Results The optimal concentration of Aβ1-42 to establish an AD HT22 cell model was 20 μmol/L,and the optimal time was 24 h.Compared with NC group,the expression of cleaved-Caspase-3 was elevated(P<0.01),NRN1 was decreased(P<0.000 1),and the expressions of SYP,MAP-2 were decreased in AD group(P<0.01).Bioinformatics analysis showed that ERK1(MAPK3)was positively correlated with APP expression(r=0.634,P<0.01)and CASP9 expression(r=0.513,P<0.05).Western blot showed that compared with NC group,the level of ERK phosphorylation was increased in AD group(P<0.01).Conclusion In the AD model of HT22 cells,neuronal injury and cell apoptosis may be achieved by activating ERK signaling pathway.