Elevated UBB+1 levels in the brain directly inhibit proteasome activity, which is thought to lead to Aβ accumulation and hyper-phosphorylated tau, and thus, constitutes a risk factor for AD (Lindsten et al., 2002; van Leeuwen et al., 2006; Shabek et al., 2009; Dennissen et al., 2010; Ciechanover and Kwon, 2015). This evidence concerns the gene UBB and Alzheimer disease.