The Y-maze test sensitively detected the onset of 5xFAD at 6 months of age as previously reported17, and two protocols of subcutaneous injection of the monoclonal anti-HMGB1 antibody completely rescued the cognitive impairment of 5xFAD mice to the level of wild type mice (Fig. 5b). This evidence concerns the gene HMGB1 and Cognitive impairment.