In addition, it was previously reported that AD patients have increased methylation in the promoter region of the dual-specificity phosphatase 22 (DUSP22) gene and downregulated DUSP22 expression, which in turn inhibited PKA-mediated tau phosphorylation and cAMP response element-binding protein (CREB) activation [100] and affected synapse plasticity and long-term memory formation [101]. This evidence concerns the gene MAPT and Alzheimer disease.