Fig 2: Statin-mediated IDE secretion from astrocytes is regulated by autophagic flux. a Lysosomal activity as determined with LysoTracker probe. Scale bar represents 10 µm. b Change in secreted IDE levels by inhibiting lysosome with bafilomycin. c & d Quantitative analysis of Fig. 3b (N = 3 experiments). Baf, bafilomycin. ** p < 0.01, # p < 0.05 vs. vehicle-treated cells

Fig 3: Schematic diagram. Statins activate autophagy via the LKB1-AMPK-mTOR signaling pathway in astrocytes, and statin-mediated IDE secretion is mediated by an autophagy-based unconventional secretory pathway. Finally, secreted IDE can significantly decrease in extracellular Aß levels, thus, modulation of this pathway can regulate AD progression by enhancing Aß clearance

Fig 4: Statin-induced AMPK activation is mediated by LKB1 in astrocytes. a Increased phosphorylation of LKB1 by treatment with simvastatin. b Statin-induced autophagy activation and IDE secretion levels in CaMKKß or LKB1 knock-downed cells. c & d Quantitative analysis of Fig. 5b (N = 3 experiments). * p < 0.05, ** p < 0.01 vs. vehicle-treated cells. n.s. indicates no significant difference

Fig 5: Statin activates autophagy via AMPK-mTOR signaling pathway in astrocytes. a Inhibition of statin-mediated autophagy activation and IDE secretion by treatment with AMPK inhibitor (Compound C; CC). b Quantitative analysis of Fig. 4a (N = 3 experiments). * p < 0.05, ** p < 0.01 vs. vehicle-treated cells; # p < 0.05, ## p < 0.01 vs. cells treated with simvastatin. c Inhibition of statin-mediated autophagy activation by treatment with compound C. Anti-LC3 antibody was used to detect autophagy. Scale bar represents 6 µm. Lower panels show figures under higher magnification. Scale bar represents 2 µm. d The effect of statins on regulation of MMP-9 and NEP levels. e Quantitative analysis of Fig. 4d (N = 3 experiments)