Lysosomal Fusion Dysfunction as a Unifying Hypothesis for Alzheimer's Disease Pathology

Figure 1

Intracellular vesicular trafficking pathways. Endocytosed surface proteins, such as APP, are delivered to the endosomal system by internalization. Internalized membrane proteins can be sorted into intralumenal vesicles of the MVB by sequential activity of ESCRTs 0, I, II, and III or delivered to the extracellular environment by the recycling endosome. Mature MVBs fuse with either the autophagosome of the autophagic pathway to form the amphisome or directly with the lysosome, which donates degradative hydrolases, creating the autolysosome where complete degradation of the sequestered material occurs. Alternatively, the multivesicular body can fuse with the plasma membrane, resulting in the exosomal secretion of the intralumenal vesicles and their internalized cargo.