Our findings are summarized as follows: (a) treatment of U‐251 astrocytes by cytokines induces the upregulation of the Ca2+‐ATPase activity of PMCA, but not that of the intracellular SERCA pump; (b) the Aβ peptide and tau (two molecular markers of AD) produce the same effects on the PMCA activity and isoform expression as cytokines; (c) all treatments induce viability reduction and an increment in apoptosis and ROS production in U‐251 astrocytes associated with their transformation to toxic A1‐like reactive astrocytes. This evidence concerns the gene MAPT and Alzheimer disease.