Alzheimerâs disease (AD) affects approximately 30-35 million people worldwide, with no disease modifying treatments currently available. AD can be classified as familial (FAD) or sporadic (SAD) with the latter being the most prevalent form (approximately 95% of cases). While FAD is due to mutations in Presenilin 1 (PSEN1), Presenilin 2 or the amyloid precursor protein (APP), the aetiology of SAD is unknown, with major risk factors including age, genetic factors and variations in allelic forms of apolipoprotein E, among others. Hallmarks of AD, including aberrant amyloid-Î² (AÎ²) production from APP leading to deposition into AÎ² plaques, tau hyperphosphorylation, increase in reactive oxygen species (ROS) and synaptic dysfunction, are present in both forms of AD. There is an urgent need to better understand the cellular mechanisms modulating these key alterations in an effort to find early identifiers for diagnosis and drug discovery. Neural cadherin (Ncad) is a cell adhesion molecule that plays a central role in maintaining synaptic plasticity, both by mediating homophilic interactions at the cell surface and modulating signalling pathways through its proteolysis. Ncad levels have been shown to be reduced in SAD and FAD human post mortem brain tissue and disruption to Ncad proteolysis has been shown in FAD and SAD brains and FAD animal models. The exact mechanism by which the disruption of Ncad function and proteolysis contribute to AD is unknown, this thesis investigates whether Ncad plays a role in modulating the key cellular mechanisms linked to AD pathogenesis: AÎ² production, ROS production and synaptic dysfunction, using induced-pluripotent stem cell (iPSC)-derived human neurons. Disrupting Ncad function, by blocking homophilic interactions through treatment with a competitive peptide (peptide A), significantly reduced full-length Ncad levels and AÎ²40 levels. However, AÎ²42 levels were unchanged, thus resulting in an increased AÎ²42/AÎ²40 ratio in both control and PSEN1 (L286V and M146L)-mutant neurons. This indicates that Ncad modulates AÎ²40 production independent of mutations in PSEN1. The increase in the AÎ²42/AÎ²40 ratio, instigated by peptide A treatment, resulted in increased ROS production in both control and PSEN1-mutant neurons. Blocking Ncad cleavage via inhibition of ADAM10 did not affect AÎ² and ROS production in control neurons, indicating that only full-length Ncad modulates these mechanisms. Furthermore, blocking Ncad function significantly reduced post-synaptic density 95 (PSD-95), whilst synaptophysin and membrane potential were unchanged in both control and PSEN1-mutant neurons. Together these results demonstrate that reduction in Ncad levels shown in FAD and SAD human post mortem brain tissue is a contributing factor to AD pathogenesis, not only by compromising synaptic stability but also by influencing AÎ² and ROS production in humans. However, the initial mechanism behind Ncad alterations occurring in AD requires further investigation. A novel finding in this thesis was that Ncad is a substrate of BACE1, thus demonstrating the importance of further investigating the molecular processing of Ncad and how it contributes to AD pathogenesis.