Transport of Amyloid beta Across the Blood-Brain Barrier

Accumulation of Amyloid beta (A-beta) peptides is thought to be one of the main causes of neurodegeneration in Alzheimer’s disease (AD). A-beta is continually produced and secreted by a variety of cell types, and circulates in the interstitial fluid, cerebrospinal fluid, and plasma. Transport of A-beta across the blood-brain barrier (BBB) is one method by which these peptides are eliminated from the brain parenchyma. A-beta efflux is mediated by multiple proteins located in the abluminal surface of vascular endothelial cells, though, the majority is facilitated by LRP-1. A-beta can also be transported from the plasma into the brain. The influx of A-beta peptides is mediated by the immunoglobulin receptor RAGE. It is not known why there is bi-directional transport of A-beta through the BBB; however, disruption of these mechanisms is thought to play a role in the pathogenesis of AD. For example, research has shown RAGE levels increase in response to the accumulation of A-beta in the brain, thereby, exacerbating A-beta aggregation. Additionally, LRP-1 expression levels in brain capillary endothelial cells are reduced during normal aging and in AD. R&D Systems offers a range of research tools needed for investigating the transport of A-beta across the BBB.