Fig. 7.

Hypothetical model of oligomeric APP-CTF-enrichment in exosomes after γ-secretase inhibition. In control conditions, C99 (blue) monomers are trafficked between the TGN and endosomes and mainly accumulate in the Golgi. However, the inhibition of γ-secretase triggers the formation of higher levels of oligomeric APP-CTFs within endosomes, the main sites of γ-secretase cleavage. These oligomers poorly bind to SorLA, thus leading to a defect in their retrograde trafficking to the TGN and misdistribution to late endosomes, lysosomes as well as to the endosome-originating exosomes. γ and β corresponds to γ-secretase and β-secretase, respectively