Functional characterization of the brain-to-blood efflux clearance of human amyloid-beta peptide (1-40) across the rat blood-brain barrier

Neurosci Res. 2006 Nov;56(3):246-52. doi: 10.1016/j.neures.2006.07.006. Epub 2006 Aug 22.


The present study sought to characterize the brain-to-blood efflux transport of human amyloid-beta peptide (hAbeta)(1-40) across the blood-brain barrier (BBB) in rats. We determined the apparent brain-to-blood [(125)I]hAbeta(1-40) efflux clearance in rats and found it to be 11.0 microL/(ming brain). There were no significant gender differences in the apparent brain-to-blood [(125)I]hAbeta(1-40) efflux clearance. The brain-to-blood [(125)I]hAbeta(1-40) efflux transport was significantly inhibited by unlabeled hAbeta(1-40) and hAbeta(1-42) by 79.1% and 36.4%, respectively, but was not inhibited by hAbeta(1-43) and hAbeta(40-1), and was significantly facilitated by hAbeta(17-40) by 16.0%, which is one of the major proteolytic fragments of hAbeta(1-40) generated by the action of Abeta degradation enzymes, such as endothelin-converting enzyme. Pre-administration of human receptor-associated protein, a low-density lipoprotein receptor-related protein (LRP) antagonist, reduced the elimination of [(125)I]hAbeta(1-40) by 20.3%, while quinidine or verapamil, P-glycoprotein (P-gp) inhibitors, did not significantly affect the elimination. Western blot analysis suggested that LRP-1 is expressed in rat brain capillary endothelial cells. In conclusion, the partial contribution of LRP-1 and the minor contribution of P-gp suggest that the hAbeta(1-40) elimination from rat brain is mediated by as yet unidentified molecules.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Amyloid beta-Peptides / pharmacokinetics*
  • Animals
  • Biological Transport / physiology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology*
  • Brain / metabolism
  • Female
  • Gene Expression / physiology
  • Humans
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Peptide Fragments / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tumor Suppressor Proteins / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Amyloid beta-Peptides
  • Iodine Isotopes
  • Peptide Fragments
  • Tumor Suppressor Proteins
  • amyloid beta-protein (1-40)