Clathrin mediated endocytosis (CME) is emerging as a critical player in the development and progression of AD in multiple brain cell types. CME is an important intersection between early neuronal dysfunction via Aβ1-42 accumulation and downstream effects that contribute to neuronal viability, such as synaptic vesicle recycling deficits and disruption of AMPAR regulation. Not only is Aβ1-42 produced following CME of APP, but internalization of multiple forms of extracellular Aβ1-42 contribute to downstream neuronal pathology. In astrocytes and microglia, which are heavily involved in clearance of extracellular Aβ1-42 in the brain, CME disruptions reduce internalization of Aβ1-42. Ultimately, CME appears to be involved in dysfunction in multiple cell types across early and late stages of AD. Thus, elucidating the mechanisms of CME and how their disruption is related to AD pathogenesis or neuroprotection in each brain cell type would both lead to a better understanding of AD mechanisms and potentially point to novel targets for the treatment or prevention of AD. In this dissertation work, I have begun to assess CME in the context of AD, using human post-mortem samples and the 5xFAD AD mouse model.