An increased understanding of the role of HMGB1 and other DAMPs, along with thrombin/PARs in the activation and transendothelial migration of piWBC contributing to neuroinflammation in AD, PD, and all neurodegenerative diseases as well as neurotrauma, may allow discovery of novel therapeutic targets and treatment strategies. This evidence concerns the gene HMGB1 and Alzheimer disease.