Dysregulated extracellular K+ could be a determinant of unhealthy brain ageing, findings in mice suggest. Whereas extracellular levels of K+ fell with age in healthy mice, they remained high in mouse models of Alzheimer disease, amyotrophic lateral sclerosis and Huntington disease. These high levels were associated with downregulation of several K+ channels or upregulation of proteins that suppress K+ uptake in astrocytes. The findings suggest that glial dysfunction leads to dysregulation of K+ levels, which could induce neuronal hyperexcitability that drives neuronal loss in disease.