CRH and major depressive disorder: Several lines of evidence from the preclinical and clinical literature have presented compelling evidence that the applications of various types of stress, sleep deprivation, administration or elevations in corticosterone or corticotropin-releasing hormone, which have all been implicated in depression, can result in significant elevation in soluble and aggregated forms of Aβ [40, 41] as well as elevation in total and phosphorylated tau [42].