Figure 1: AβPP trafficking and amyloidogenic processing Fulllength AβPP is synthesized in the endoplasmic reticulum (ER), transported to Golgi/trans-Golgi network (TGN), and inserted into the plasma membrane via secretory vesicles. Cell surface AβPP can be re-internalized to endosomes from which AβPP can either be recycled back to the cell surface or can be delivered to lysosomes for degradation. When AβPP is internalized into endosomes, the acidic environment if favorable for increased activities of BACE-1 and γ- secretase and stimulation of Aβ production. Endosome-derived Aβ can be degraded in lysosomes by cathepsins. Un-degraded Aβ can either be accumulated in endolysosomes or released to extracellular spaces via exocytosis.