Viral gene delivery of NEP to the brain of AD transgenic mice also was shown to reduce amyloid pathology (Marr et al., 2003) and subsequent studies, including the application of a recombinant, brain-targeted NEP (Spencer et al., 2014), have confirmed and extended these observations on the critical nature of NEP to amyloid clearance (Leissring et al., 2003). This evidence concerns the gene MME and Alzheimer disease.