Furthermore, there is a reduction and down-regulation in the activities of Aβ degrading proteases neprilysin (NEP), insulin degrading enzyme (IDE) and angiotensin converting enzyme (ACE) already in the early stages of AD, partly due to reactive oxygen species although this decline in enzyme activity also occurs during normal aging (Savaskan et al., 2001; El-Amouri et al., 2008). Here, MME is linked to Alzheimer disease.