Cellular stress, BACE1 and Aβ production are involved in a toxic vicious cycle in AD. Various cellular dysfunctions including oxidative stress, inflammation and calcium homeostasis disturbance occur in AD-affected brains. These alterations activate the transcription of the stress-induced β-secretase BACE1 that contributes to Aβ production. Once yielded at supra-physiological levels, Aβ induces cellular stresses that, in turn activate BACE1, therefore setting up a vicious cycle. Such self-maintained toxicity can lead to cellular cell death. Brain insults like hypoxia and traumatic brain injury contribute to this scheme by inducing cellular stress.