TNF-α/TNFR1 signaling initiates neuronal necroptosis via RIPK1/RIPK3/MLKL cascade. Impaired autophagy flux due to UVRAG downregulation leads to p62 accumulation, which exacerbates necroptosis in AD. TNFR1 knockdown or UVRAG overexpression reduces p-MLKL levels, inhibiting necroptosis. This evidence concerns the gene MLKL and Alzheimer disease.