Moreover, loss of long-term memory, a clinical symptom in AD, was further aggravated by intracerebroventricular injection of HMGB1; however, this effect was blocked by TLR4 antagonist injection in RAGE-deficient mice, indicating that HMGB1-induced memory dysfunction is TLR4- and RAGE-dependent [18]. The gene discussed is TLR4; the disease is Alzheimer disease.