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

Shingo Ito, Sumio Ohtsuki, Tetsuya Terasaki

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

The present study sought to characterize the brain-to-blood efflux transport of human amyloid-β peptide (hAβ)(1-40) across the blood-brain barrier (BBB) in rats. We determined the apparent brain-to-blood [125I]hAβ(1-40) efflux clearance in rats and found it to be 11.0 μL/(min g brain). There were no significant gender differences in the apparent brain-to-blood [125I]hAβ(1-40) efflux clearance. The brain-to-blood [125I]hAβ(1-40) efflux transport was significantly inhibited by unlabeled hAβ(1-40) and hAβ(1-42) by 79.1% and 36.4%, respectively, but was not inhibited by hAβ(1-43) and hAβ(40-1), and was significantly facilitated by hAβ(17-40) by 16.0%, which is one of the major proteolytic fragments of hAβ(1-40) generated by the action of Aβ 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 [125I]hAβ(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 hAβ(1-40) elimination from rat brain is mediated by as yet unidentified molecules.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
JournalNeuroscience Research
Volume56
Issue number3
DOIs
Publication statusPublished - 2006 Nov 1

Keywords

  • Alzheimer's disease
  • Aβ degrading enzyme
  • Efflux transport
  • Gender difference
  • LRP-1
  • P-gp

ASJC Scopus subject areas

  • Neuroscience(all)

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