Using the CK-p25 mouse model (overexpressing p25 (a truncated version of p35) that aberrantly activates cyclin-dependent kinase 5 (Cdk5)), compelling studies by the Tsai laboratory have provided mechanistic insights about the epigenetic dysregulation of histone acetylation that contributes to impaired synaptic plasticity, neurodegeneration and cognitive decline in AD [113,114,115,116,117,118]. The gene discussed is CDK5; the disease is Alzheimer disease.