P-glycoprotein (Pgp) is directly linked to amyloid-β (Aβ) metabolism in vivo according to researchers at Washington University School of Medicine and the University of Rochester, USA.“Pgp contributes to efflux of Aβ peptide out of the brain, which suggests that differential function of Pgp could contribute to the pathogenesis of Alzheimer’s disease”, says corresponding author David Holtzman. Efflux transport of Aβpeptide across the blood–brain barrier seems to be an important pathway for removal of CNS-derived Aβ. Pgp is an ATP-dependent transport protein highly expressed on the luminal surface of brain capillary endothelial cells where it constitutes a major component of the blood–brain barrier. Pgp plays a critical part in preventing molecules and drugs from entering the CNS. Furthermore, researchers have shown that Pgp could have a role in cellular uptake of Aβ. Holtzman’s group used Pgp-null mice to show that Aβ removal from the brain is also partly mediated by Pgp.

To assess the differential role of Pgp in transport of Aβ across the blood–brain barrier, Holtzman and colleagues microinjected iodine-125-labelled Aβ40 or Aβ42 in to the brains of Pgp-null mice and controls (J Clin Invest 2005; published online Oct 20. DOI: 10. 1172/JCI25247). The researchers also coadministered carbon-14-labelled inulin to measure bulk flow of interstitial fluid in the same mice. Mice