The receptor for advanced glycation end-products (RAGE) is a multiligand membrane receptor that has been implicated in the cytotoxicity effects of β-amyloid protein (Aβ) in AD. Positive feedback mechanism of RAGE within blood-brain barrier (BBB) and/or cells inside the brain are proposed, including interaction with Aβ stimulate activation of proinflammatory cytokines, release of reactive oxygen species (ROS), which leads to neuron damage and BBB dysfunction. RAGE is the main factor mediating Aβ cytotoxicity. Attenuation of RAGE activity may inhibit Aβ from accumulation in the cerebral and prevent neurotoxicity. Furthermore, RAGE may serve as a therapeutic target for Alzheimer's disease by inhibiting pathophysiological consequences of Aβ-RAGE interaction. Tight junctions (TJ) identified as the basic structure of the BBB, and RAGE mediated Aβ cytotoxicity to the brain microvascular endothelial cells (BMEC), resulted in damaged BBB structural integrity. However, the potential mechanism is poor studied.