Rapid and Direct Transport of Cell Surface APP to the Lysosome defines a novel selective pathway

Background A central feature of Alzheimer's disease is the cleavage of the amyloid precursor protein (APP) to form beta-amyloid peptide (Aβ) by the β-secretase and γ-secretase enzymes. Although this has been shown to occur after endocytosis of APP from the cell surface, the exact compartments of APP processing are not well defined. We have previously demonstrated that APP and γ-secretase proteins and activity are highly enriched in purified rat liver lysosomes. In order to examine the lysosomal distribution and trafficking of APP in cultured cells, we generated constructs containing APP fused to a C-terminal fluorescent protein tag and N-terminal HA-epitope tag. These were co-transfected with a panel of fluorescent-protein tagged compartment markers.