Taken together, our results (Figs. 2–6) suggest a potential link between chronically dysregulated pancreatic amylin and impaired rat Aβ efflux from the brain into the systemic circulation through mechanisms that involve: 1, amylin vasculopathy leading to reduced cerebral vasodilation and altered interstitial fluid drainage along the walls of cerebral blood vessels; and 2, amylin-induced endothelial dysfunction leading to P-gp and LRP1 downregulation at the BBB. This evidence concerns the gene PGP and endothelial dysfunction.