The Role of the ATP-Binding Cassette Transporter P-Glycoprotein in the Transport of β-Amyloid Across the Blood-Brain Barrier

Silke      Vogelgesang; Gabriele      Jedlitschky; Anja      Brenn; Lary      C. Walker

Abstract

The blood-brain barrier (BBB) protects the brain against endogenous and exogenous compounds and plays an important part in the maintenance of the microenvironment of the brain. In particular, the importance of brain-to-blood transport of brain-derived metabolites across the BBB has gained increasing attention as a potential mechanism in the pathogenesis of neurodegenerative disorders such as Alzheimers disease, which is characterized by the aberrant polymerization and accumulation of specific misfolded proteins, particularly β-amyloid (Aβ). There is growing evidence that the ABC transport protein P-glycoprotein (P-gp), a major component of the BBB, mediates the efflux of Aβ from the brain. In this review, we discuss the possible role of P-gp in Alzheimers disease and other neurodegenerative disorders, and consider how a fuller understanding of this function might promote the development of more effective treatment strategies.

Keywords: β-amyloid, P-glycoprotein, Alzheimer's disease, neurodegeneration, blood-brain barrier, Creutzfeldt-Jakob disease, aging, autopsy, immunotherapy, Microglia