Synaptic dysfunction in response to amyloid-beta (Aß) accumulation is increasingly recognized as a precursor of cognitive decline in Alzheimer's Disease (AD). AMPA receptors (AMPARs), the major neurotransmitter receptors in the brain, are implicated in the synaptic dysfunction observed in rodent models expressing amyloidogenic APP mutations. AMPARs are proposed to undergo aberrant trafficking, characterized by changes in their subunit composition and subcellular localization. The precise mechanisms underlying the dysregulation of AMPAR trafficking in AD remain poorly understood.Here, we apply molecular biology and imaging techniques to hiPSC derived neurons carrying the clinically-relevant London amyloidogenic APP (V717I) mutation to investigate AMPAR subunit composition, trafficking, and the role of AMPAR interacting proteins in this process. We demonstrate that APPV717I neurons express lower levels of AMPAR subunits GluA2 and GluA3, but increased levels of GluA1, compared to controls. We also uncover changes in the expression levels and post-translational modifications of proteins involved in regulating the recycling or lysosomal targeting of specific AMPAR subunit combinations. We are currently investigating subunit-specific AMPAR trafficking in hiPSC neurons. So far, these changes suggest a disruption in calcium homeostasis and synaptic strength caused by aberrant AMPAR trafficking in AD. To further elucidate the importance of these molecular interactions, we will employ CRISPR gene editing and interfering peptides as interventions in the APPV717I hiPSCs to potentially restore normal AMPAR trafficking. Hence, this approach aims to shed light on potential therapeutic targets to alleviate synaptic deficiencies and, ultimately, arrest cognitive decline early in the disease progression.