HMGB-1 blockade using neutralizing antibodies has been repeatedly shown to be beneficial for brain ischemia and TBI (Okuma et al., 2012; Wang C. et al., 2016), to prevent BBB disruption in a model of Alzheimer’s disease (Festoff et al., 2016), reduce 6 hydroxy-dopamine induced neuronal death (Sasaki et al., 2016) and to reduce neuroinflammation and neurocognitive dysfunction in the aged brain (Fonken et al., 2016; Terrando et al., 2016). Here, HMGB1 is linked to Alzheimer disease.