Reactive astrocytes and neuroinflammation are well-known features of Alzheimer’s disease that are associated with disease manifestation, pathology and brain atrophy. Despite a compelling association with Alzheimer’s disease, the impact of reactive astrocytes on disease progression or their therapeutic potential remains unknown. The goal of this project is to clarify the contribution of reactive astrocytes to the pathogenesis of Alzheimer’s disease. Knowledge of the involvement of astrocytes may be the key to delaying or preventing neuronal cell death. This research team previously discovered a complex composed of two players—the ion pump Alpha2-Na/K ATPase and the protein Alpha-Adducin—that promote a neurotoxic response and are present in reactive astrocytes. In the proposed study, we will investigate the role of the Alpha2-Na/K ATPase and Alpha-Adducin complex in Alzheimer’s disease. The underlying goal will be to determine whether pharmacological inhibition of this complex is beneficial in Alzheimer’s disease.