Nature Reviews Neuroscience, Published online: 21 May 2026; doi:10.1038/s41583-026-01053-1 Neuronal loss in a mouse model of Alzheimer disease occurs through necroptosis and is shown to be dependent on low-glucose conditions, which increase hyperphosphorylated tau levels; in turn, this simultaneously activates pro-necroptotic pathways and disables a key checkpoint mechanism.