At the organ level, DAMP-induced TLR signaling drives pathology across systems: TLR4 activation accelerates atherosclerosis, HMGB1 promotes plaque instability, and microglial TLR4 activation by HMGB1 or S100 proteins fuels neuroinflammation and cognitive decline [64,65]. This evidence concerns the gene HMGB1 and Mental deterioration.