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J Neurochem. 2010 Jun;113(5):1356-63. doi: 10.1111/j.1471-4159.2010.06708.x. Epub 2010 Mar 26.

Lack of brain-to-blood efflux transport activity of low-density lipoprotein receptor-related protein-1 (LRP-1) for amyloid-beta peptide(1-40) in mouse: involvement of an LRP-1-independent pathway.

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  • 1Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan.

Abstract

The contribution of low-density lipoprotein receptor-related protein-1 (LRP-1) to the brain-to-blood amyloid-beta peptide (A beta) efflux transport across the blood-brain barrier (BBB) remains controversial. The purpose of the present study was to clarify whether or not LRP-1 plays a role in efflux transport of A beta at the BBB. After microinjection of [(125)I]activated alpha2-macroglobulin (alpha 2M), a typical LRP-1 ligand, into mouse secondary somatosensory cortex region under ketamine-xylazine anesthesia, residual radioactivity was not significantly decreased up to 90 min, whereas after microinjection of [(125)I]human A beta(1-40) [hA beta(1-40)], the residual radioactivity decreased time-dependently. Co-administration of receptor-associated protein, an inhibitor of LRP-1, did not influence [(125)I]hA beta(1-40) elimination from mouse brain, suggesting that members of the LDL receptor gene family, including LRP-1, do not contribute to hA beta(1-40) elimination from mouse brain across the BBB. There was no significant difference between the uptakes of [(125)I]activated alpha 2M and [(14)C]inulin by mouse brain slices, suggesting that activated alpha 2M was not significantly bound to and/or taken up by parenchymal cells. In conclusion, our results show that LRP-1 does not play a significant role in the brain-to-blood efflux transport of A beta(1-40) at the mouse BBB, but an unidentified transporter(s) appears to be involved.

PMID:
20367755
[PubMed - indexed for MEDLINE]
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