Recent reports have documented BACE1 as a stress-induced protease [169, 170, 172, 174, 185-187], and in view of the apparent importance of metabolic dysfunction and amyloidosis in AD, it is worth noting that BACE1 upregulation has been observed under a variety of conditions including hypoxia, energy disruption and/or mitochondrial stress (discussed below). This evidence concerns the gene BACE1 and Alzheimer disease.