Tai, Leon M.; Loughlin, A. Jane; Male, David K. and Romero, Ignacio A.
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),
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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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