J. Neurochem. (2010) 113, 1356–1363.

The contribution of low‐density lipoprotein receptor‐related protein‐1 (LRP‐1) to the brain‐to‐blood amyloid‐β peptide (Aβ) 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 Aβ at the BBB. After microinjection of [¹²⁵I]activated α2‐macroglobulin (α2M), 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 [¹²⁵I]human Aβ(1–40) [hAβ(1–40)], the residual radioactivity decreased time‐dependently. Co‐administration of receptor‐associated protein, an inhibitor of LRP‐1, did not influence [¹²⁵I]hAβ(1–40) elimination from mouse brain, suggesting that members of the LDL receptor gene family, including LRP‐1, do not contribute to hAβ(1–40) elimination from mouse brain across the BBB. There was no significant difference between the uptakes of [¹²⁵I]activated α2M and [¹⁴C]inulin by mouse brain slices, suggesting that activated α2M 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 Aβ(1–40) at the mouse BBB, but an unidentified transporter(s) appears to be involved.