These results indicate that in the sequence of events of microglial and astrocytic activation that were proposed to lead to neuronal damage in Alzheimer’s disease based on in vitro studies, the increase of Cx43 hemichannel activity in astrocytes is a deleterious process and this is confirmed in an in vivo model that selectively manipulates connexins in astrocytes. The gene discussed is GJA1; the disease is early-onset autosomal dominant Alzheimer disease.