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

The clearance of amyloid beta (Abeta) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphate-binding cassette transporters to the clearance of Abeta through the blood-brain barrier. Therefore, we...

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Bibliographic Details
Published in:Journal of cerebral blood flow and metabolism 2009-06, Vol.29 (6), p.1079
Main Authors: Tai, Leon M, Loughlin, A Jane, Male, David K, Romero, Ignacio A
Format: Article
Language:English
Online Access:Get full text
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Summary:The clearance of amyloid beta (Abeta) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphate-binding cassette transporters to the clearance of Abeta through the blood-brain barrier. Therefore, we investigated whether Abeta could be a substrate for P-glycoprotein (P-gp) and/or for breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. Inhibition of P-gp and BCRP increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to (125)I Abeta 1-40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Abeta 1-40 from entering the brain.
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.2009.42