biostudies-literatureDing FSimon FoundationLundbeck FoundationsNovo NordiskNCCIH NIH HHSNIA NIH HHSAdelson Medical Research FoundationNHLBI NIH HHSCNS2, IncNINDS NIH HHSNational Institutes of HealthU.S. Army Research OfficeNIH HHS1726-1739https://www.ebi.ac.uk/biostudies/studies/S-EPMC11068329biostudies-literatureUnknown147(5)Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral scleroBrain : a journal of neurologyDysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.PMC11068329R01AT012312R01 NS110776R01 AT011439MURI W911NF1910280R01AT011439U19 NS128613R01 AG072298R01 AT012312R01 HL122578R01HL122578Ding FWeikop PRasmussen RNSun QGoldman SAPeng SXu QKang NNedergaard MSong WLong CfalseDysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration.Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal ageing. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury as K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this distinction. Here we measured the cortical extracellular K+ concentration ([K+]e) in awake wild-type mice as well as murine models of neurodegeneration using K+-sensitive microelectrodes. Unexpectedly, aged wild-type mice exhibited significantly lower cortical [K+]e than young mice. In contrast, cortical [K+]e was consistently elevated in Alzheimer's disease (APP/PS1), amyotrophic lateral sclero2024-01-01T00:00:00Z2024 May2026-04-30T03:20:06.59Z2025-04-05T23:52:10.627ZS-EPMC110683293846258910.1093/brain/awae075