Our results add to these findings by implicating raised BACE1 activity and manipulation of APP processing as central to these enzyme deficits and metabolic adaptations at the cellular level, indicating a key role for BACE1 and its up-regulation in response to oxidative and inflammatory stress, which are associated with the very early stages of AD (Nunomura et al., 2001; Zhang et al., 2007; Guglielmotto et al., 2009). Here, APP is linked to Alzheimer disease.