AGER and Alzheimer disease: In the AD brain, Aβ could be transported into the brain across the BBB and it is regulated by the BBB receptors and transporters.61, 62 Aβ accumulation in AD brain results from decreased clearance from BBB and increase of uptake from the circulatory system.61, 62 RAGE transports Aβ from the circulation into the brain,63, 64 whereas LRP-1 is related with rapid clearance of Aβ from the brain to blood.65, 66, 67, 68 The dysfunction of LRP-1 weakens the ability of BBB to clearing Aβ.