Our discovery that post-AIE treatment with the selective HMGB1 inhibitor glycyrrhizic acid rescues AIE-induced acceleration of AD-associated increases in proinflammatory HMGB1 neuroimmune signaling, microglial activation, and persistent reductions of basal forebrain cholinergic neurons in adult 5xFAD female mice support neuroinflammation as critical to the development and progression of AD. This evidence concerns the gene HMGB1 and Alzheimer disease.