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Article type: Research Article
Authors: Do, Tuan Minha | Bedussi, Beatriceb | Chasseigneaux, Stéphanieb | Dodacki, Agnèsb | Yapo, Cédricb | Chacun, Hélènec | Scherrmann, Jean-Michelb | Farinotti, Roberta | Bourasset, Fanchonb; *
Affiliations: [a] Laboratoire de pharmacie clinique et pharmacocinétique, EA 4123, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France | [b] INSERM U705, UMR CNRS 8206, Université Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques, Paris, France | [c] UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France
Correspondence: [*] Correspondence to: Fanchon Bourasset, PharmD, PhD, INSERM U705, CNRS UMR 8206, Université Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques, 4 avenue de l'Observatoire 75270 Paris Cedex 06, France. Tel.: +33 1 53 73 98 59; Fax: +33 1 40 05 43 42; E-mail: [email protected].
Abstract: The influx of amyloid-β peptide (Aβ) 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 Clup of [3H]Aβ while L-thyroxine increased it (5.5-fold). We demonstrated an interaction between Aβ 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 Aβ is partly mediated by Oatp1a4 and that L-thyroxine may play a crucial role in the inhibition of brain Aβ clearance.
Keywords: Alzheimer's disease, amyloid-β peptide, blood-brain barrier, in situ brain perfusion, L-thyroxine, Oatp1a4, rosuvastatin
DOI: 10.3233/JAD-121891
Journal: Journal of Alzheimer's Disease, vol. 36, no. 3, pp. 555-561, 2013
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