Figure 6. Proposed model of LRP1 involvement in the trafficking of APP and Aβ production.
Fe65 bridges LRP1 and APP via cytoplasmic domain interactions, resulting in enhanced delivery of APP into endosomal compartments where BACE and PS1 are known to reside. Here, regulated intramembrane proteolysis of APP occurs, generating the Aβ peptide and releasing its intracellular domain. The APP intracellular domain forms a multimeric complex with Tip60 and Fe65, diffuses to the nucleus and modulates gene expression, including suppression of LRP1 gene transcription. The Aβ peptide is released into the media in recycling vesicles.