MDR1-P-Glycoprotein (ABCB1) Mediates Transport of Alzheimer's amyloid-beta peptides--implications for the mechanisms of Abeta clearance at the blood-brain barrier

Brain Pathol. 2007 Oct;17(4):347-53. doi: 10.1111/j.1750-3639.2007.00075.x. Epub 2007 Jul 4.


Amyloid-beta (Abeta) is the major component of the insoluble amyloid plaques that accumulate intracerebrally in patients with Alzheimer's disease (AD). It has been suggested that MDR1-P-glycoprotein (ABCB1, P-gp) plays a substantial role in the elimination of Abeta from the brain. In the present study, MDR1-transfected LLC cells growing in a polarized cell layer were used to characterize the interaction of Abeta1-40/1-42 with P-gp. In this system, P-gp-mediated transport can be followed by the efflux of the fluorescent dye rhodamine-123, or of Abeta itself from the cells into the apical extracellular space. Abeta significantly decreased the apical efflux of rhodamine-123, and the transcellular transport of Abeta1-40 and Abeta1-42 into the apical chamber could be demonstrated using both ELISA and fluorescence (FITC)-labeled peptides. This transport was inhibited by a P-gp modulator. Furthermore, ATP-dependent, P-gp-mediated transport of the fluorescence-labeled peptides could be demonstrated in isolated, inside-out membrane vesicles. Our data support the concept that P-gp is important for the clearance of Abeta from brain, and thus may represent a target protein for the prevention and/or treatment of neurodegenerative disorders such as AD.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain / metabolism*
  • Brain / physiopathology
  • Cell Compartmentation / physiology
  • Cell Membrane / metabolism
  • Endothelial Cells / metabolism
  • Extracellular Space / metabolism
  • LLC-PK1 Cells
  • Metabolic Clearance Rate / physiology
  • Peptide Fragments / metabolism
  • Peptides / metabolism
  • Protein Transport / physiology
  • Rhodamine 123 / metabolism
  • Swine
  • Transfection
  • Transport Vesicles / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Peptides
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Rhodamine 123