Here, we show for the first time that ANP32A negatively regulates the expression of a set of synaptic proteins including glutamate receptor subunits GluR1, GluR2, NR2A and NR2B, and as well as Syp and Syn1 via suppressing histone acetylation and ANP32A elevation is associated with cognitive impairment in an AD model. Here, SYP is linked to Alzheimer disease.