This study investigated the functional role of astrocytes in Alzheimer’s disease progression. We measured astrocytic K+ clearance in the hippocampus and somatosensory cortex of a mouse model of AD during disease development. Our results show that astrocytic [K+]o clearance in the hippocampus is reduced in symptomatic 5xFAD mice, and this decrease is region-specific. The decrease in [K+]o clearance correlated with reduction in the expression and conductivity of Kir4.1 channels and a decline in the number of primary connected astrocytes. Moreover, astrocytes in the hippocampus of symptomatic 5xFAD mice demonstrated increased reactivity which was accompanied by an increased excitability and altered spiking profile of nearby neurons. These findings indicate that the supportive function astrocytes typically provide to nearby neurons is diminished during disease progression, which affects the neuronal circuit signalling in this area and provides a potential explanation for the increased vulnerability of neurons in AD. This dataset contains 7 prism spreadsheets and 87 images describing the astrocytic clearance rate, morphology and electrophysiological properties recorded during disease progression of AD. The images contained in this dataset are published open access. The full dataset is not available for open publishing due to ethics approval conditions. To discuss the data, please contact Yossi Buskila ORCID 0000-0001-8500-469X