In the presence of a caspase inhibitor and a SMAC mimetic, which extrinsically recapitulates our observations in the AD brain, TNF stimulation of iPSC derived human glutamatergic neurons led to the activation of necroptosis by increasing the pMLKL expression in the cytoplasm, which was reversed by RIPK1, RIPK3, or MLKL inhibitors. Here, RIPK1 is linked to Alzheimer disease.