β-Amyloid precursor protein trafficking. β-Amyloid precursor protein (APP) matures through the constitutive secretory pathway from the endoplasmic reticulum to the plasma membrane (PM). The majority of APP is then quickly internalized into early endosomes, where APP is recycled back to the PM or targeted to the lysosomal degradation pathway. Nonamyloidogenic processing (green) mainly occurs at the cell surface, where α-secretase is particularly enriched. Amyloidogenic processing (red) involves APP trafficking through the secretory and recycling pathways where APP interacts with β- and γ-secretases. Amyloid-β (Aβ) is mainly generated in the trans-Golgi network where the γ-secretase complex is enriched.