Alzheimers disease(AD)is a progressive neurodegenerative disorder which develops over the course of multiple decadess and as a result of the accumulation of the pathogenic β-amyloid peptide(Aβ).Autophagy is an essential degradation pathway in clearing abnormal protein aggregates in mammalian cells and is responsible for protein homeostasis and neuronal health.Deficits in the autophagy result in protein aggregation,the generation of toxic protein species,and accumulation of dysfunctional organelles,which are hallmarks of AD.Fuling,the sclerotium of Poria cocos(Schw.)Wolf,was the most frequently used in the dementia intervention in TCM formulae over the past 10 centuries.However,the mechanism of prevention and treatment of AD have not well elucidated yet.Based on previous results,Dehydropachymic acid,an effective constituent in Poria cocos,was screened to study the effect on the Aβ clearance in Bafilomycin A1 treated PC12 cells.DPA could significantly decreases the Aβ1-42 content in the culture medium and eliminate the intracellular accumulation of APP and Aβ1-42 in Bafilomycin A1 induced PC12-APP cells.For the detailed mechanisms,the effects of DPA on the LC3Ⅱ/LC3Ⅰ ration,GFP-labeled LC3 puncta,the internal pH in lysosome and the amount of mCatD were further investigated and the results showed that DPA could restore the lysosomal acidification and recovery the autophgic flux which is impaired by Bafilomycin A1.In conclusion,our study discovered that DPA could effectively clear the accumulation of Aβ1-42 in bafilomycin A1 impaired PC12 cells and highlighted its therapeutic potential for AD treatment.