Editors' ChoiceAlzheimer’s Disease

Tickets, Please

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Science Translational Medicine  31 Aug 2011:
Vol. 3, Issue 98, pp. 98ec141
DOI: 10.1126/scitranslmed.3003108

Permission to participate in an exclusive gathering is restricted to those holding a backstage pass—a VIP ticket, if you will. Bouncers monitor the doors in order to limit general access to the event, turning away suspect characters. In a similar manner, access to the brain is limited by the blood-brain barrier, which is selective in its transport of therapeutic agents. Tight junctions between the capillary endothelial cells, efflux proteins, and several enzymes prevent a number of molecules from passing easily into the brain.

The overproduction and aggregation of amyloid-β peptide (Aβ) in the brain—called plaque formation—has been implicated in the progression of Alzheimer’s disease. Although recent reports have shown that liposomes containing phosphatidic acid can bind Aβ with high affinity, the challenge remains to grant these liposomes access across the blood-brain barrier so as to remove the plaques. To this end, Re et al. modified the surface of these nanoliposomes with a 10–amino acid fragment of apolipoprotein E (ApoE), which is recognized by the low-density lipoprotein receptor (LDLr). Not only does LDLr promote the transcellular transport of macromolecules, but the expression of LDLr is also higher in the blood-brain barrier as compared with other endothelia in the body.

Using fluorescently labeled ApoE liposomes and human brain endothelial cells (hCMEC/D3), Re and colleagues demonstrated that liposomes decorated with an ApoE peptide fragment gained entrance into the cells, whereas unmodified liposomes were denied access. Radiolabeling confirmed the observation of increased cellular uptake of ApoE-liposomes into hCMEC/D3 cells. Importantly, the presence of the ApoE peptide fragment did not prevent the phosphatidic acid–containing nanoliposomes from binding to Aβ, thus suggesting a potential strategy to sequester peripheral Aβ. For those seeking a promising lead in treating Alzheimer’s disease, this may be just the ticket.

F. Re et al., Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide. J. Biotechnol. 6 July 2011 (10.1016/j.biotec.2011.06.037). [Abstract]

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