Indeed, it is of the utmost importance to emphasize that the best way to approach the prevention and treatment of unconventional AD is to perform the transient composite BACE activation/ISR inhibition therapy (or utilize directly acting iAβ degradation agents instead of BACE activators in this approach) in conjunction with the reduction or removal of unconventional stressors capable of eliciting the neuronal integrated stress response via the elimination of their source. This evidence concerns the gene BACE1 and Alzheimer disease.