Dementia currently affects over 46.8 million people, with Alzheimers disease (AD) accounting for 50-75% of all cases. There are no disease modifying treatments and the aetiology that drives disease is still relatively unknown. Amyloid-beta (Abeta) is hypothesised to be a main proponent behind AD pathogenesis, where Abeta aggregation and deposition results in neuronal cell death, and eventually brain atrophy, cognitive decline, and death. Support for this amyloid hypothesis is demonstrated by inherited, familial AD (fAD) cases, where mutations result in increased production of Abeta, and/or the more aggregate prone Abeta 42. However, the majority of cases are sporadic (sAD) and there is evidence to suggest that impaired Abeta degradation rather than increased production results in Abeta deposition. iPSCs offer the opportunity to model human disease from affected patients. Currently most studies utilising iPSC-derived neural models have focussed on neurons, and on patients affected by fAD. These studies have demonstrated increased Abeta levels, whereas studies that have used iPSC-neurons to model sAD do not always demonstrate increased Abeta production. This suggests that degradation of Abeta is impaired, but proteolytic degradation of Abeta has not been investigated in these cells. Furthermore, there may be other cell types involved, whose roles have not been as well characterised, or other environmental factors that are initiating disease onset in sAD. The data in this thesis shows that iPSC-neurons and iPSC-astrocytes can be generated, and a way in which proteolytic Abeta degradation can be measured using fluorescently tagged Abeta. Insulin-degrading enzyme (IDE) was shown to be the largest contributor to Abeta degradation in both iPSC-neurons and astrocytes. Hypoxia is increased in the brain in ageing and in AD, and this environmental risk factor was applied to control and sAD iPSC-neurons. The data suggested not only increased Abeta production was occurring in response to hypoxia, but that Abeta degradation and IDE expression and localisation were also affected. The data in this thesis also demonstrated that primary human astrocytes can be made activated and hypoxic. Astrocytes exposed to hypoxia demonstrated similar effects in the levels and degradation of Abeta compared to the iPSC-neurons. Furthermore when neurons were cultured in the conditioned media collected from hypoxic astrocytes, iPSC-neurons exhibited higher levels of Abeta 42. Altogether the data presented in this thesis has shown that environmental cell stressors such as hypoxia are relevant to disease pathogenesis in these cells, and that not only is Abeta production affected, but Abeta degradation is also altered. This understanding of how environmental risk factors and different cell types can contribute to sAD pathology, will help better model the aetiology of disease, and ultimately lead to improved therapeutic targets.