This shows that increased levels of danger/damage-associated, proinflammatory molecules (the alarmin DAMPs, HMGB1 and S100B, as well as Aβ) feature prominently in the AD continuum from normal aging through MCI by acting on TLRs and RAGE to induce neuroinflammatory signaling at the BBB endothelium. This evidence concerns the gene S100B and Alzheimer disease.