Together, our findings support that BDNF/TrkB scarcity in AD elicits C/EBPβ upregulation by the p-JAK2/p-STAT3 pathway activated by inflammatory cytokines, and active C/EBPβ subsequently escalates δ-secretase expression that mediates APP and Tau pathological processing, culminating in massive neuronal cell loss. Here, STAT3 is linked to Alzheimer disease.