For example, SENP3 gene expression is markedly reduced in brain samples either from healthy aged subjects (Lu et al, 2004) or from Alzheimer's disease patients (Weeraratna et al, 2007), and SENP3 levels are altered in brain samples from the patients with Down's syndrome (Binda et al, 2017), which is associated with premature ageing and is a risk factor for dementia development (Roth et al, 1996; Weksler et al, 2013). This evidence concerns the gene SENP3 and early-onset autosomal dominant Alzheimer disease.