engEmery, Brett AddisonKhanzada, ShahrukhHu, XinMaggi, Maria AnnaBisti, SilviaAmin, HayderNetwork-Level Characterization of Hippocampal Disruptions in Alzheimer's Disease Using Large-Scale Electrophysiology.Alzheimer Disease: physiopathologyHippocampus: physiopathologyHippocampus: pathologyAnimalsMiceMice, TransgenicDisease Models, AnimalMicroelectrodesElectrophysiology: methodsNerve Net: physiopathologyHumansAlzheimer's disease (AD), a progressive neurodegenerative disorder, is projected to affect over 130 million people globally by 2050. While extensive efforts have focused on targeting molecular hallmarks such as amyloid-beta (Aβ) plaques and tau pathology, network-level dysfunction remains a critical but underexplored component of AD progression. Disruptions in hippocampal-cortical (HC) circuit activity emerge early in AD, compromising memory processing and cognitive functions. Characterizing these disruptions requires high-resolution platforms capable of capturing network-wide spatiotemporal dynamics. To address this, we implemented a high-density microelectrode array (HD-MEA) biosensor to assess large-scale electrophysiological activity in ex vivo hippocampal slices from well-established APPNL and APPNL-G-F mouse models. Our approach quantifies hippocampal oscillatory disturbances and examines their modulation by saffron, a natural compound with reported neuroprotective properties. Results indicate that hippocampal network activity is progressively impaired in APPNL-G-F mice, particularly in sharp-wave ripple (SWR) and multi-unit activity (MUA) patterns. The HD-MEA platform provides a scalable tool for investigating AD-associated network dysfunctions and exploring potential modulatory interventions.IEEE 1-4 (2025). doi:10.1109/EMBC58623.2025.11253272info:eu-repo/semantics/conferenceObjectinfo:eu-repo/semantics/publishedVersion2025 47th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) : [Proceedings] - IEEE, 2025. - ISBN 979-8-3315-8618-8 - doi:10.1109/EMBC58623.2025.112532722025 47th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) : [Proceedings] - IEEE, 2025. - ISBN 979-8-3315-8618-8 - doi:10.1109/EMBC58623.2025.11253272<br/>47th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC, Copenhagen, Denmark, 2025-07-14 - 2025-07-18IEEE2025info:eu-repo/semantics/closedAccessDEhttps://pub.dzne.de/record/285809https://pub.dzne.de/search?p=id:%22DZNE-2026-00345%22Researchersinfo:eu-repo/semantics/altIdentifier/pmid/pmid:41335966info:eu-repo/semantics/altIdentifier/doi/10.1109/EMBC58623.2025.11253272