Although the latter is a common argument made in support of the metals hypothesis (Bush et al., 1994b; Atwood et al., 1998; Huang et al., 1999; Barnham et al., 2003a), aged rats can exhibit neuritic plaques (Vaughan and Peters, 1981) and a number of AD-related functional, morphological and behavioral changes are observed in wild type rats and mice if clearance of murine Aβ is impaired by the pharmacological inhibition or genetic ablation of Aβ degrading/clearing enzymes such as neprilysin (NEP) and ATP-binding cassette C1 (Iwata et al., 2000; Madani et al., 2006; Krohn et al., 2015). This evidence concerns the gene MME and Alzheimer disease.