The findings that exercise (running wheel), indomethacin (a direct anti-inflammatory drug), and galantamine and donepezil (anti-cholinesterase drugs) block the AIE-induced increases in proinflammatory HMGB1-TLR-RAGE signaling and loss of neurogenesis and cholinergic neurons as well as cognitive deficits, supporting HMGB1-TLR-RAGE signaling as a mechanism of AIE-induced AUD-like pathology. The gene discussed is AGER; the disease is Cognitive impairment.