Although future studies should investigate in detail the antioxidant role of sRAGE in preventing HMGB1–RAGE-induced pro-inflammatory processes and exacerbated oxidative stress, the findings suggest that sRAGE was significantly affected by alcohol use and abstinence and should be considered as a potential biomarker of ethanol toxicity-induced cognitive impairment. The gene discussed is HMGB1; the disease is Cognitive impairment.