In addition, many studies using mouse models with AD have reported that decreased emotional or social interactions exacerbate AD-related pathologies and cognitive impairment (Pietropaolo et al., 2009; Huang et al., 2011, 2015); however, the application of social interactions in an mouse model with AD decreased histone deacetylase 2 (HDAC2) expression and occupancy of HDAC2 in the promoter region of brain-derived neurotrophic factor (BDNF) exon IV, resulting in upregulated BDNF expression in the hippocampus region through increased acetylation of H3K9 and H4K12 histones. Here, HDAC2 is linked to Cognitive impairment.