HMGB1 and Alzheimer disease: Research has demonstrated the presence of toll-like receptor 4 (TLR4) overexpression in patients with AD.[55] TLR4 overexpression enhances the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and its downstream mediators, leading to diffuse neuritis in the brain.[56] It also activates the expression of high-mobility group protein box 1 (HMGB1) and receptor for advanced glycation end products.