For example, exposure to excess Amyloid-Beta causes diminished Brain-Derived Neurotrophic Factor (BDNF) signaling in AD patient tissue and mouse models (Peng et al., 2005); however, this diminution can be reversed by the overexpression of the de-ubiquitinating enzyme UCHL-1, which, through an unknown mechanism, restores the trafficking of BDNF receptors (Poon et al., 2013). This evidence concerns the gene BDNF and Alzheimer disease.