(62az) Role of P-Glycoprotein in the Transport of Amyloid-β Protein in Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA), a cerebrovascular deposition of the amyloid-Β (AΒ) protein, is a well-known cause of hemorrhagic stroke. Altered AΒ transport may be responsible for vascular AΒ accumulation. However, it remains unclear how the transport of AΒ from the brain to the vasculature is impeded to facilitate AΒ accumulation. P-glycoprotein (Pgp), an ATPase transporter, interacts with amphipathic molecules and mediates their removal from the brain. It was hypothesized that Pgp is involved in the transport of AΒ through the BBB. AΒ assembly state(s) transported from the basolateral to the apical side of confluent monolayers of human brain microvascular endothelial cells were compared using endothelial permeability coefficients (Pe). Both AΒ monomer and AΒ aggregates were transported across monolayers. In addition, AΒ assembly state(s) that interact with Pgp were identified using an in vitro assay that measures ATPase activity of Pgp. These results revealed that Pgp preferentially binds soluble AΒ aggregates, but not monomer of fibril. Together, these findings suggest a role for Pgp I transporting soluble AΒ aggregates across the BBB.