Alzheimer’s disease (AD) has wide-ranging health and economical impact affecting millions globally. The molecular mechanisms behind AD are not yet understood, but alterations in the processing and clearance of Amyloid precursor protein (APP), such as increased levels of specific APP fragments like Amyloid-ß peptide (Aß), have been observed in early-stage AD. Increased Aß concentration leads to impaired long-term potentiation (LTP) at hippocampal CA1-CA3 synapses, the process that can be restored by partially blocking GluN2B-NMDA receptor (Ronicke et al., Neurobiol. Aging 2011). We modeled computationally the effects of Aß-induced alterations in synaptic plasticity in a hippocampal CA1-CA3 network of 100 CA1 pyramidal neurons with inhibitory interneurons and inputs from medial septum, entorhinal cortex and Schaffer collaterals from CA3 neurons. We employed a novel NMDAR-dependent voltage-based synaptic plasticity model (Dainauskas et al., Front. Comput. Neurosci. 2023), implementing experimentally observed effects of accumulated Aß on LTP at CA1-CA3 synapses. The results illustrate that altered LTP impairs the pattern storage and recall of the network, which is recovered by partial blockage of GluN2B-NMDA receptor. This study integrates the effect of AD-related peptides at molecular, synaptic and network level, explaining how AD effects memory functions in hippocampal networks.Acknowledgement: Research Council of Lithuania, Agence Nationale de la Recherche (Flagship ERA-NET Joint Transnational Call JTC 2019 with Human Brain Project, No. S-FLAG-ERA-20-1/2020-PRO-28), Horizon Europe (Specific Grant Agreement No.101147319, EBRAINS 2.0), Swiss National Supercomputing Centre (CSCS) under project ID ich002; Italian National Recovery and Resilience Plan (NRRP), M4C2, funded by NextGenerationEU (Project IR0000011, CUP B51E22000150006, EBRAINS-Italy)