S100A9 and Alzheimer disease: Here, by using combined analysis of ex vivo AD-affected brain tissues and modeling S100A9 aggregation and co-aggregation with Aβ in vitro, we demonstrate the direct involvement of S100A9 in AD basic mechanisms from the perspective of its intrinsic amyloidogenicity, ability to form plaques and neurotoxicity, thus bridging the AD neuroinflammatory and amyloid cascades.