Abstract: Objective To investigate changes in amyloid precursor protein (APP) and tau gene expression in hippocampus of rat with long-term lead exposure.Methods Female and male (at the ratio of 2:1) specific-pathogen free Sprague-Dawley rats were randomly divided into three groups:control group supplied with distilled water,low lead exposure group (LLG) with drinking water containing lead acetate of 800 mg/L,and high lead exposure group (HLG) with drinking water containing lead acetate of 1 000 mg/L.Then the male offsprings were continuously exposed to drinking water containing lead acetate of 0 mg/L (control group),300 mg/L (LLG),and 900 mg/L (HLG)mg/L and lead content in blood and hippocampus tissue of the offsprings were measured at postnatal week 3 (PNW3),postnatal week 41 (PNW41) and postnatal week 70 (PNW70);the mRNA and protein expressions of tau and APP in hippocampus of the offsprings were determined simultaneously with real-time quantitative PCR(qPCR)and Western blot.Results Compared with those of the control group,the lead content of blood and hippocampus were significantly increased in lead-exposed male offsprings (P < 0.05).The expression of APP mRNA(1.398±0.827) and protein (1.454±0.190) were significantly up-regulated in PNW70 male hippocampus of offsprings in HLG (P < 0.05).Compared with those of the control group,the expression of tau protein of the offsprings in LLG (4.850±1.257) and HLG (5.557±1.880)were significantly increased at PNW3 (P < 0.01),and the expression of phosphorylated tau protein (3.225±1.098) increased in male offspring's hippocampus of HLG at PNW70 (P < 0.05).Conclusion Long-term lead exposure induces up-regulations of mRNA and protein of APP and tau in hippocampus of rats at PNW3 and PNW70.