In vitro discrimination of the role of LRP1 at the BBB cellular level: Focus on brain capillary endothelial cells and brain pericytes

Several studies have demonstrated that the blood-brain barrier (BBB) (dynamic cellular complex composed by brain capillary endothelial cells (BCECs) and surrounded by astrocytic end feet and pericytes) regulates the exchanges of amyloid p (All) peptide between the blood and the brain. Deregulation of these exchanges seems to be a key trigger for the brain accumulation of A beta peptide observed in Alzheimer's disease (AD). Whereas the involvement of receptor for advanced glycation end-products in A beta peptide transcytosis has been demonstrated in our laboratory, low-density lipoprotein receptor's role at the cellular level needs to be clarified. For this, we used an in vitro BBB model that consists of a co-culture of bovine BCECs and rat glial cells. This model has already been used to characterize low-density lipoprotein receptor-related peptide (LRP)'s involvement in the transcytosis of molecules such as tPA and angiopep-2. Our results suggest that A beta peptide efflux across the BCEC monolayer involves a transcellular transport. However, the experiments with RAP discard an involvement of LRP family members at BCECs level. In contrast, our results show a strong transcriptional expression of LRP1 in pericytes and suggest its implication in A beta endocytosis. Moreover, the observations of pericytes contraction and local downregulation of LRP1 in response to A beta treatment opens up perspectives for studying this cell type with respect to A beta peptide metabolism and AD. (C) 2014 Elsevier B.V. All rights reserved.