BDNF and Alzheimer disease: In AD, calcium dysregulation leads to increased degradation of PKA subunits through excessive activation of calpain, which reduces PKA activity and subsequently downregulates the phosphorylation of transcription factor cAMP response element binding protein (CREB) and BDNF expression.247–249 Moreover, Aβ42-treatment interferes with BDNF-induced activation of other pro-survival Ser/Thr kinases such as PI3K/Akt and ERK.250