Nevertheless, our results have clearly demonstrated the roles of endothelial Sirt1-mediated HMGB1 regulation in neuronal amyloidosis and imply that endothelial injury by vascular risk factors might be an important target to prevent amyloid pathogenesis in the development of AD, in which Sirt1 activity in both endothelia and neurons might be important. This evidence concerns the gene HMGB1 and Alzheimer disease.