Objective To investigate the role of Wnt/β-catenin pathway in the glucocorticoids (GC)-mediated Alzheimer' s disease-like pathological changes in vitro.Methods Human embryonic kidney 293 (HEK293/wt) cells stably transfected with the longest human tau (tau441,HEK293/tau) and wild-type HEK293 cells were employed to study the role of GC.Cell viabilities of the two cell lines were examined by cell counting kit-8 ( CCK-8 ).Levels of phosphorylated tau ( p-T205 ) and dephosphorylated tau (Tau-1),β-catenin,phosphorylated β-catenin (p-β-catenin),glycogen synthase kinase-3β (GSK-3β),phosphorylated GSK-3β at Ser9 (ps9-GSK-3β) and Bcl-2 were determined by Western blotting.Results Treatment with 1 μmol/L GC for 48 h decreased the viability of HEK293/wt and HEK293/tau cells to 95.5％ ±3.2％ and 77.8％ ± 4.4％ (t =6.60,P ＜ 0.05 ).Moreover,GC treatment decreased the levels of ps9-GSK-3β,Tau-1,β-catenin and Bcl-2 to 47.8％ ± 10.4％,53.9％ ± 11.7％,50.9％ ±7.6％,48.4％ ±6.5％ of control groups ( t =7.01,3.86,7.09,7.30,all P ＜ 0.05 ),and increased the relative levels of pT205,p-β-catenin to 180.5％ ± 22.2％,201.3 ％ ± 27.6％ of control groups (t =5.51,5.27,both P ＜0.05) only in HEK293/tau cells.Finally,LiCI efficiently prevented the above effects of GC in HEK293/tau cells.Conclusion GC may trigger Alzheimer' s disease-like pathological changes by inhibiting the Wnt/β-catenin pathway and these pathological processes seem to specifically depend on the presence of human tau.