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Although mechanisms remain incompletely understood, hyperactivity downstream of soluble amyloid beta (A\u03b2) is strongly implicated in synapse degeneration. Engulfment of synapses by reactive astrocytes was observed in end\u2010stage disease tissue, particularly around plaques. Due to astrocytes' role in synaptic modulation, we hypothesised that astrocytes could modulate synapse degeneration downstream of soluble A\u03b2 earlier in disease pathogenesis. To test this, we challenged organotypic mouse brain slices with human\n                    <jats:sc>AD<\/jats:sc>\n                    brain homogenates containing A\u03b2. Changes in synaptic activity were detected 2\u2009h after A\u03b2 challenge, and spine loss was seen after 24\u2009h. We observe that A\u03b2\u2010containing homogenate induces a significant loss of spines compared with controls. A\u03b2\u2010containing homogenate also causes a significant increase in the frequency of synaptic calcium events, particularly in synapses lost at 24\u2009h. Dendritic spines associated with astrocytic processes were significantly more likely to survive at 24\u2009h after A\u03b2 challenge and had reduced levels of externalised phosphatidyl serine despite no effect of astrocyte proximity on synaptic activity. Inhibiting astrocytic glutamate transporters prevented the protective effects of astrocytes on synapses, indicating that astrocytes are protective of synapses at least in part through removing excess glutamate from the synaptic microenvironment. Our findings suggest that an organotypic mouse brain slice model challenged with disease tissue homogenates effectively recapitulates key features of early AD, including synapse loss and hyperexcitability. Moreover, they indicate that astrocytes play a protective role in preserving synapses, particularly during short\u2010term exposure to low concentrations of toxic A\u03b2. Future work is needed to elucidate the role of astrocyte\u2010mediated synapse phagocytosis in response to chronic A\u03b2 exposure.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70480","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T13:41:05Z","timestamp":1774705265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Astrocyte Proximity Protects Synapses From Human Amyloid\u2010Beta Induced Degeneration in a Mouse Ex\u00a0Vivo Model of Early Alzheimer's Disease"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-929X","authenticated-orcid":false,"given":"Francesco","family":"Gobbo","sequence":"first","affiliation":[{"name":"Institute for Neuroscience and Cardiovascular Research and UK Dementia Research Institute University of Edinburgh  Edinburgh 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