This study investigates the role of extracellular potassium ([K⁺]e) in distinguishing healthy ageing from neurodegenerative diseases. The authors measured [K⁺]e in the cortex of wild-type mice and murine models of Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS, SOD1G93A), and Huntington's disease (R6/2). They found that aged wild-type mice exhibited lower [K⁺]e than young mice, while [K⁺]e was elevated in the disease models. [K⁺]e correlated inversely with neuronal density and positively with predicted neuronal firing rate. Astrocytic potassium channel genes were downregulated in disease models but not in normal ageing. Specifically, Kcnj10, an inwardly rectifying potassium channel, was downregulated in ALS and Huntington's disease models, while Fxyd1 and Slc1a5, which regulate potassium uptake, were upregulated in Alzheimer's disease and ALS models. The study suggests that dysregulation of extracellular [K⁺]e homeostasis in neurodegenerative diseases may be due to aberrant astrocytic potassium buffering, highlighting the role of glial dysfunction in neurodegeneration.This study investigates the role of extracellular potassium ([K⁺]e) in distinguishing healthy ageing from neurodegenerative diseases. The authors measured [K⁺]e in the cortex of wild-type mice and murine models of Alzheimer's disease (APP/PS1), amyotrophic lateral sclerosis (ALS, SOD1G93A), and Huntington's disease (R6/2). They found that aged wild-type mice exhibited lower [K⁺]e than young mice, while [K⁺]e was elevated in the disease models. [K⁺]e correlated inversely with neuronal density and positively with predicted neuronal firing rate. Astrocytic potassium channel genes were downregulated in disease models but not in normal ageing. Specifically, Kcnj10, an inwardly rectifying potassium channel, was downregulated in ALS and Huntington's disease models, while Fxyd1 and Slc1a5, which regulate potassium uptake, were upregulated in Alzheimer's disease and ALS models. The study suggests that dysregulation of extracellular [K⁺]e homeostasis in neurodegenerative diseases may be due to aberrant astrocytic potassium buffering, highlighting the role of glial dysfunction in neurodegeneration.