Objective Alzheimers disease (AD) is the most common neurodegenerative disorder.Abnormal amyloid β(Aβ) accumulation in the brain is one of the major factors which may result in AD.Aβ accumulation level in the brain was dependent on the balance between Aβ production and clearance.We showed previously that cathepsin B-cystatin C axis played key roles in Aβ metabolism of transgenic mice overexpressing hAPP with Swedish and Indiana mutation.However, it is not clear if the cathepsin B-cystatin C axis could affect Aβaccumulation in mice overexpressing wild type hAPP, which accounts for more AD cases compared with mutant hAPP.In the present study, we want to investigate the effects of cathepsin B and cystatin C deletion on Aβ in mice with wild type hAPP.Methods Animals were obtained by crossing hAPPwt mice (line I63) with cathepsin B-/-or cystatin C-/-.ELISA and western blot analyses were used to measure Aβ levels and hAPP fragments, respectively.We also used immunohistochemistry to detect pathology induced by Aβ.Results (1) Cathepsin B or cystatin C ablation did not affect hAPP processing.(2) Cathepsin B or cystatin C ablation affected Abeta levels in mice with wild type hAPP.Conclusion Cathepsin B-cystatin C axis played key roles in Aβ metabolism of transgenic mice overexpressing mutant and wild type hAPP.