Objective:To study the changes in the expression of ATP-binding cassette transporter A1(ABCA1)protein-transported cholesterol in the hippocampus and liver of rapidly aging mice,and to provide a theoretical basis for the treatment of Alzheimer's disease(AD)by strengthening the spleen and benefiting the qi method.Methods:Eight three months-old SAMR1 mice were used as the normal group,and 32 three months-old SAPM8 mice were divided into model group,western medicine group,low-dose group and high-dose group,8 mice in each group,and the western medicine group was gavaged with Donepezil(0.013 mg/mL),while the low-dose group and the high-dose group were gavaged with Sijunzi Decoction(3.59,28.72 mg/mL).The mice were tested for memory in the Morris water maze;the changes in the expression of fatty acid synthase(FASN)in the liver and apolipoprotein E(APOE)in the hippocampus were detected by immunohistochemistry,the total cholesterol,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the plasma were detected by ELISA.The expression changes of flotillin-1,ABCA1,LDLR protein in the liver and flotillin-1,ABCA1 and APOE protein in the hippocampus were detected by Western Blot.Results:Compared with the normal group,the mice in the model group significantly increased latent escape time and significantly decreased crossing times(P<0.01);serum total cholesterol significantly increased and HDL cholesterol significantly decreased(P<0.01);hepatic FASN protein expression and hippocampal APOE protein expression increased(P<0.01);expression of liver flotillin-1 protein,ABC AI and LDLR protein significantly increased(P<0.01),expression of hippocampal flotillin-1 and APOE protein significantly increased(P<0.01),and expression of ABCA1 protein significantly decreased(P<0.01).Compared with the model group,the low-and high-dose groups significantly decreased latent escape time and significantly increased crossing times(P<0.05),serum total cholesterol significantly increased and HDL cholesterol significantly increased(P<0.01);hepatic FASN,LDLR protein expression and hippocampal APOE protein expression significantly decreased(P<0.01),and ABCA1 protein expression in the high dose group decreased(P<0.01);hippocampal flotillin-1 and APOE protein protein expression significantly decreased(P<0.01)and ABCA1 protein expression significantly increased(P<0.01).Conclusion:Sijunzi Decoction can improve the memory function of SAMP8 mice and treat AD,and the mechanism may be related to the correction of central and peripheral cholesterol transport disorder by regulating the function of ABCA1 protein in the liver and hippocampus.