Oatp1a4 and an L-Thyroxine-Sensitive Transporter Mediate the Mouse Blood-Brain Barrier Transport of Amyloid-β Peptide

The influx of amyloid-beta peptide (A beta) across the blood-brain barrier is partly mediated by the receptor for advanced glycation end products (RAGE). But other transporters, like Oatp (organic anion transporter polypeptide, SLC21) transporters, could also be involved. We used in situ brain perfusion to show that rosuvastatin and taurocholate, two established Oatp1a4 substrates, decreased (5-fold) the Cl-up of [H-3]A beta while L-thyroxine increased it (5.5-fold). We demonstrated an interaction between A beta and Oatp1a4 by co-immunoprecipitation and western blotting experiments, supporting the hypothesis that the rosuvastatin- and taurocholate-sensitive transporter was Oatp1a4. In conclusion, our results suggest that, in mice, the brain uptake of A beta is partly mediated by Oatp1a4 and that L-thyroxine may play a crucial role in the inhibition of brain A beta clearance.