We found that cognitive impairment could be reversed with long-term administration of 7,8-DHF, a TrkB receptor agonist, which could activate AKT/GSK3β signaling pathway as well as suppress expression of active-AEP, and then display its remarkable protective effects by decreasing production of tau N368 and phosphorylated tau at serine 396. The gene discussed is GSK3B; the disease is Cognitive impairment.