**4. Conclusions**

The hydrophobic and membrane-anchored nature of the intraneuronally-generated Aβ peptide suggests that simple diffusion, as it has until now been assumed, does not adequately explain the mechanism of its expulsion into the extracellular space. Data presented here provide compelling evidence to substantiate the ability for P-gp to export Aβ. This not only occurs at the BBB endothelium, but for the first time, we have shown that the clearance of Aβ out of neurons is also an active process mediated by P-gp. Further studies are still needed to examine whether modulating P-gp function affects markers of neurodegeneration in vivo, and to confirm if this is a viable avenue to pursue in the search for effective AD therapies. Nonetheless, clarifying the molecular mechanisms involved in the pathway of the Aβ peptide, from its synthesis in the cell to clearance from the brain, is critical for our understanding of the pathophysiology of AD.
