We observed that KXS upregulated AKT phosphorylation, suppressed GSK3β and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. The gene discussed is TLR4; the disease is Cognitive impairment.