β-Amyloid efflux mediated by p-glycoprotein
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 76, Issue 4, pages 1121–1128, February 2001
How to Cite
Lam, F. C., Liu, R., Lu, P., Shapiro, A. B., Renoir, J.-M., Sharom, Frances J. and Reiner, P. B. (2001), β-Amyloid efflux mediated by p-glycoprotein. Journal of Neurochemistry, 76: 1121–1128. doi: 10.1046/j.1471-4159.2001.00113.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received August 25, 2000; revised manuscript received October 13, 2000; accepted October 13, 2000.
- ABC transporter;
- Alzheimer's disease;
A large body of evidence suggests that an increase in the brain β-amyloid (Aβ) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Aβ, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-binding cassette (ABC) transporter, is an Aβ efflux pump. Pharmacological blockade of p-gp rapidly decrease extracellular levels of Aβ secretion. In vitro binding studies showed that addition of synthetic human Aβ1–40 and Aβ1–42 peptides to hamster mdr1-enriched vesicles labeled with the fluorophore MIANS resulted in saturable quenching, suggesting that both peptides interact directly with the transporter. Finally, we were able to directly measure transport of Aβ peptides across the plasma membranes of p-gp enriched vesicles, and showed that this phenomenon was both ATP- and p-gp-dependent. Taken together, our study suggests a novel mechanism of Aβ detachment from cellular membranes, and represents an obvious route towards identification of such a mechanism in the brain.