Imaging, and monitoring treatment of, amyloid pathology by MRI

3 year PhD studentship, fully funded by The Alzheimer’s Society

The project aims to utilise optimised imaging techniques for the early detection and diagnosis of Alzheimer’s disease. It builds on our recent findings concerning the mechanism of amyloid-beta synaptotoxicity, and further testing of the drug fasudil, which has shown to protect synapses and cognition, and reduce amyloid-beta production and plaque formation in a mouse model of Alzheimer’s disease.

Alzheimer’s disease (AD) is defined by the presence of amyloid plaques and neurofibrillary tangles, with accompanying brain atrophy and vascular dysfunction, which manifest as cognitive and behavioural disturbances that worsen as the disease progresses. This project will use advanced imaging techniques, including structural and functional MRI, to characterise early- and late- stage brain dysfunction in a “state-of the art” rat model of AD, which, uniquely, features all the above pathologies.

This project will determine if by treating the rat model with fasudil, we can not only improve cognition and reduce brain pathology but that we can also visualize this using non-invasive and translational imaging techniques. For this, transgenic rats will be treated with fasudil at two timepoints, during early and late stages of the disease, and imaged by MRI immediately afterwards. Behavioural and neurochemical analyses will also be conducted. We predict that imaging will reveal functional deficits at the early timepoint, and functional and structural changes at the late timepoint with both being attenuated by fasudil. The project will thus generate novel, non-invasive translatable and cost-effective methodologies to detect and diagnose AD and a means to monitor potential disease modifying treatments.