In contrast, we revealed that during pTau-induced chronic neuronal death, IκB phosphorylation and the nuclear translocation of p65 are both modulated by the RIPK1–RIPK3–MLKL axis, indicating that necroptotic machinery protein likely acts upstream of IKK to directly promote IKK phosphorylation and IκBα degradation, and finally initiating the activation of NF-κB during neuronal necroptosis in AD. Here, RIPK1 is linked to Alzheimer disease.