P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-β

Tai, Leon M.; Loughlin, A. Jane; Male, David K. and Romero, Ignacio A. (2009). P-glycoprotein and breast cancer resistance protein restrict apical-to-basolateral permeability of human brain endothelium to amyloid-β. Journal of Cerebral Blood Flow and Metabolism, 29(6) pp. 1079–1083.

DOI: https://doi.org/10.1038/jcbfm.2009.42

Abstract

The clearance of amyloid beta (Aβ) from the brain represents a novel therapeutic target for Alzheimer’s disease. Conflicting data exists as to the contribution of ATP binding cassette transporters to the clearance of Aβ through the blood-brain barrier. We therefore investigated whether Aβ could be a substrate for P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. P-gp and BCRP inhibition increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to 125I Aβ 1-40. Our in vitro data suggest that P-gp and BCRP might act to prevent blood-borne Aβ 1-40 entering the brain.

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