In recent days, HMGB1 has emerged as an extracellular target against a diverse range of CNS disorders with HMGB1 involvement, including AD [15], PD [18], MS [96], Epilepsy [97], TBI [12], SAH [13], etc. Moreover, HMGB1 targeted therapy conferred neuroprotective effects against these diseases mainly by inhibiting its expression and release, blocking its translocation, and down-regulating the expression of inflammatory molecules. This evidence concerns the gene HMGB1 and Alzheimer disease.