Alzheimer's disease (AD) is characterized by excessive cerebrovascular depositio n of the -amyloid peptide (A).

The investigation of A transport across the lood- r ain arrier (BBB) has een hindered y inherent limitations in the cellular syst ems currently used to model the BBB, such as insufficient arrier properties and poor reproduci ility. In addition, many of the existing models are not of human or rain origin and are often arduous to esta lish and maintain. Thus, we chara cterized an in vitro model of the BBB employing human rain microvascular endoth elial cells (HBMEC) and evaluated its utility to investigate A exchange at the l ood- rain interface. Our HBMEC model offers an ease of culture compared with pri mary isolated or coculture BBB models and is more representative of the human r ain endothelium than many of the cell lines currently used to study the BBB. In our studies, the HBMEC model exhi ited arrier properties compara le to existing BBB models as evidenced y the restricted permea ility of a known paracellular marker. In addition, using a simple and rapid fluormetric assay, we showed that antagonism of key A transport proteins significantly altered the i-directional t ranscytosis of fluorescein-A (1-42) across the HBMEC model. Moreover, the magnitu de of these effects was consistent with reports in the literature using the same ligands in existing in vitro models of the BBB. These studies esta lish the HBM EC as a representative in vitro model of the BBB and offer a rapid fluorometric method of assessing A exchange etween the periphery and the rain. or more information on the Roskamp Institute and Alzheimers please visit: http://www.mullanalzheimer.com http://www.mullanalzheimer.info http://www.michaelmullan.us www.rfdn.org