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Yet, early impact of sex on neuronal activity and microglia in the hippocampus, a main site of memory formation and one of the most vulnerable brain areas in AD, remains poorly understood. We thus assessed these issues by using APPPS1 mouse model of AD\u2010like amyloid pathology at a pre\u2010symptomatic stage (5\u20136\u2009months). Our electrophysiological data point to opposite alterations in hippocampal CA1 neurons' basal glutamatergic neurotransmission and response to excitatory inputs between male and female APPPS1 mice. These complex changes in neuronal activity are likely to precede plasticity impairments, which do not yet translate into sexual dimorphism of Long\u2010Term Potentiation (LTP) at the studied age. Alteration in synaptic transmission in males coincides with an increased number and coverage of microglia, together with increased plaque coverage, as compared to the female hippocampus. Such increased microgliosis in males is accompanied by complex sex\u2010related differences in the expression of specific transcriptomic markers Disease\u2010Associated Microglia (DAM)\/Microglial neurodegenerative phenotype (MGnD), whereas homeostatic (M0) markers were unaffected. Our data show for the first time that subtle alterations in hippocampal neuronal activity coincide with early sex\u2010related differences in amyloidosis and microglia already at the pre\u2010symptomatic stage of AD\u2010like pathology.<\/jats:p>","DOI":"10.1002\/glia.70029","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T09:00:11Z","timestamp":1746003611000},"page":"1727-1745","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Subtle Alterations in Hippocampal Neuronal Activity Coincide With Early Sex\u2010Specific Differences in Amyloidosis and Microglia in a Pre\u2010Symptomatic Mouse Model of Alzheimer\u2010Like Pathology"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3399-0747","authenticated-orcid":false,"given":"Thomas","family":"Chaigneau","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Centre de 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