Consequences of blood-brain barrier dysfunction in Alzheimer’s disease on therapeutic drug delivery

The BBB is a crucial defence system that protects the brain from the entry of unwanted molecules. Additionally, the BBB poses a major obstacle for drug delivery into the brain for brain disorders like Alzheimer’s disease, the most common cause of dementia. Alzheimer’s disease is associated with a dysfunctional BBB indicated by changes in BBB cell function and altered physiological conditions in the vicinity of the BBB. The altered BBB in Alzheimer’s disease likely affects drug delivery efficiency and drug effects in the brain; however, this is not fully understood.

This project will investigate using patient-derived induced pluripotent stem cell (iPSC) models the consequences of BBB dysfunction in Alzheimer’s disease on drug delivery efficiency, with a focus on oxidative stress, a key feature of BBB dysfunction. Specifically, BBB cell models will be generated from iPSCs obtained from people with Alzheimer’s disease and characterised for differences in oxidative stress and mitochondria-related pathways in comparison to healthy control models. Differences in the ability to deliver Alzheimer’s therapeutics (such as amyloid-beta targeting antibodies) between Alzheimer’s and healthy BBB will be compared. Finally, it will be investigated if targeting disease-associated pathways, such as oxidative stress, can improve drug delivery across the BBB and improve neuron health (the affected cells in Alzheimer’s). This project is expected to improve our understanding of key mechanisms that contribute to BBB dysfunction in Alzheimer’s disease, reveal novel insights into the effects of BBB dysfunction on drug delivery and improve the development of new BBB-crossing Alzheimer’s therapeutics.

This scholarship is part of the MIND-AD CRE Scholarship program, which will support three students across its advertised projects. Applicants will be required to submit an online application and attend an interview.