Neuronal network imbalance and synaptic dysfunction both critically contribute to cognitive decline in AD. Network imbalance is increasingly recognized as an early characteristic of AD, which might precede and drive clinical symptoms. Early alterations in parvalbumin (PV+) interneurons contribute to this network dysfunction in AD mouse models. However, to what extent this shapes how memories are stored within the brain and drives cognitive decline remains to be determined. Our objective is to investigate synaptic, local, and network imbalances in AD, as well as their mutual dependence.We used APPswe/PS1dE9 mice crossed with Arc::dVenus mice that express destabilized Venus fluorescent protein (dVenus) under the control of transgenic Arc promoter to visualize the memory engram. 24 hours after contextual fear conditioning, we found significantly lower freezing levels in APPswe/PS1dE9 mice compared to WT littermates. In parallel, the reactivation of the training engram by re-exposing the mice to the fearful context was reduced in the hippocampal dentate gyrus of APPswe/PS1dE9 mice. In WT mice, PV expression in the dorsal CA1 was anti-correlated to the freezing levels.We aim to elucidate the role of Aβ-driven changes in PV-interneurons on memory engram processing and behavior using fiber photometry. We utilized eGRASP to investigate changes in synaptic interactions in the memory engram microcircuit. Finally, we investigate network activity using electromyography, electrocorticography, and local field potential recordings of the cortex and hippocampus in APPswe/PS1dE9 mice.In conclusion, these results show that Aβ-mediated pathology impairs memory and, specifically, engram reactivation, which may result from changes in PV-interneurons.