Nuclear accumulation of HDAC4 has been observed in human Alzheimer’s disease post-mortem brains as well as the brains of Alzheimer’s mice with the abundance of nuclear HDAC4 correlating with increased clinical dementia scores in humans (Herrup et al., 2013; Shen et al., 2016), indicating that excess abundance of nuclear HDAC4 impairs cognitive function. This evidence concerns the gene HDAC4 and early-onset autosomal dominant Alzheimer disease.