In this thesis, we investigated the impact of Alzheimer’s disease on neuronal function and glial cells. Hereto we used various models, i.e. the APPswePS1dE9 AD mouse model, human post-mortem brain material, and a microglia-like cell model. In a review we focused on the role of reactive astrocytes in the AD mouse model, indicating that reactive astrocytes can be a promising treatment target in AD. Using the same mouse model, we investigated changes in neuronal function at various ages. We concluded that aging has a more prominent effect on the measurements than the increased presence of amyloid. In a first experiment, to investigate the potential role of microglia in AD, we used a microglia-like model to examine the effect of Aβ1-42 oligomers on transcriptomic changes. Interestingly, we observed a distinct upregulation of metallothionein subtypes in the Aβ1-42 oligomer stimulated cells. The upregulation of metallothioneins could have a neuroprotective function against the oxidative stress and neuroinflammation involved in AD, indicating that the acute activation by Aβ1-42 oligomers could induce a protective response. We characterized the Aβ plaque burden and morphology in cortical brain slices of AD patients and non-demented control with amyloid plaques. Even though the last group has overall less Aβ plaques, relatively more dense-core plaques were observed. We found no differences in the total number of microglia or morphology between the groups. Further characterization of plaque-associated microglia suggested a reduced phagocytic activity by microglia surrounding dense-core plaques in NDC+-cases. No difference in synaptic density between AD- and NDC+-cases near dense-core or diffuse plaques was detected.