In addition, Aβ42, as well as Aβ 23–35, have been known to disrupt the blood-brain barrier (BBB) and further increase AD risk by binding to Receptor for Advanced Glycosylation End products (RAGE), down-regulating tight junction proteins, and increasing reactive oxygen species (ROS)-mediated damage in endothelial cells [98,99]. This evidence concerns the gene AGER and Alzheimer disease.