Alzheimer’s disease (AD) is an increasingly common neurodegenerative disease, with global prevalence set to reach 100 million by 2050. Extracellular amyloid plaques are one of the histopathological hallmarks associated with AD. These extracellular aggregates predominantly comprise of amyloid-ß, which is the product of dysfunctional amyloid precursor protein (APP) processing. Most pharmaceutical research to date has focused on targeting amyloid-ß deposits, however, the lack of clinical success has prompted the field to re-examine the associated cell biology.

The endolysosomal system is important in regulating the complexities of physiology at the cellular, tissue, and organism levels. Changes to this system are often detected decades prior to the clinical onset of AD symptoms. Analysis of post-mortem brain extracts isolated from AD patients has characterised enlarged ‘swollen’ endosomes as a defining phenotype of this disorder. Hence, investigation of the relationship between endosomal swelling and AD is essential for a more detailed understanding of AD aetiology. My project aims to further our understanding of how the endolysosomal system regulates APP processing and how perturbations to this system contribute to disease pathology, to facilitate improved diagnosis and treatment of AD.