Therefore, UBB+1 is involved in both secretase-dependent and independent pathways for Aβ generation and this could be a reasonable explanation as to why UBB+ conjugated protein aggregation has been found to be associated with Aβ plaques in transgenic UBB+1 AD brain (van Leeuwen et al., 2006; Zhang et al., 2007; El Ayadi et al., 2012). This evidence concerns the gene UBB and Alzheimer disease.