Fig. 2.

Scheme of the increased endocytic production of Aβ due to LOAD genetic risk factors. ApoE4-mediated increase in APP endocytosis and/or via increased APP in the secretory pathway due to increased APP transcription; Bin1 loss-of-function impedes BACE1 to recycle out of sorting endosomes; Sorla loss-of-function decreases APP recycling out of endosomes to the TGN; CD2AP loss-of-function decreases APP sorting into MVBs and lysosomal degradation; CALM loss-of-function increases APP and γ-secretase endocytosis and delivery to sorting endosomes; PLD3 loss-of-function affects lysosome morphology and perhaps APP processing at endosomes