FIGURE 8.

Diagram of the pathways underlying the up‐regulation of Aβ production by abnormalities in early endosomes, under high glucose conditions. High glucose increased PICALM, AP2A1, and CHC expression through ROS‐stimulated Sp1 nuclear translocation. PICALM facilitates clathrin‐mediated APP endocytosis at lipid rafts, which induces early endosomal enlargement. On the one hand, high glucose impairs endosomal clearance via AMPK/mTORC1‐ and ROS‐mediated auto‐lysosomal dysregulation. The consequences of abnormalities in early endosomes are overproduction of Aβ and cognitive impairment