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Investigating the link between amyloid-β oligomers, neuroinflammation and cognitive deficits in preclinical models for Alzheimer’s Disease


Project Description

Currently four out of the five pharmacological treatments used for Alzheimer’s disease (AD) are acetylcholinesterase inhibitors aimed at boosting the amount of acetylcholine in the brain, with the fifth being an N-methyl-D-aspartate (NMDA) receptor antagonist. These treatments are purely symptomatic and it is clear they have no significant effect on the prevention or delay of disease progression.

The Amyloid Cascade hypothesis suggests that in both familial and sporadic AD, amyloid beta (Aβ) accumulation in the brain is the primary culprit in driving AD pathology. In order to better understand the mechanisms of AD, and to test possible drugs and molecular targets, a number of models have been created for aspects of the disease. By far the most common method is the use of animal models, specifically transgenic rodent models. Alongside these are models where Aβ is infused into rodent brains. The infusion can be either acute, with a single injection, or using a cannula, chronic. Together these models have been invaluable in identifying downstream mechanisms involved in the early phase of the disease process and have started to highlight novel targets for drug development.

Microglia, the brains resident immune cells, respond to inflammatory insults such as Aβ by producing pro-inflammatory cytokines and free radicals. It is hypothesised that this results in synaptic damage and triggers the cascade leading to cognitive deficits and neuronal loss.

In the current proposal will investigate the effect of Aβ oligomers on microglial activation and subsequent behavioural and pathological deficits in different preclinical models for AD research.

Our overall aim is to establish and characterise the link between Aβ oligomers and subsequent deficits in a rat model for Alzheimer’s disease research and utilise this model for assessing novel disease modifying therapeutic interventions.

The student will undertake Modules 1-4 of the Home Office training for working with animals. They will receive training in conducting and analysing different cognitive tasks alongside post-mortem analysis of rodent and human tissue for different neuroinflammatory and neuronal markers.
Training will also be provided in methods of data collection, statistical analysis and graphical presentation. Oral presentation skills will be developed through presentation of the results at internal laboratory meetings and both national and international conferences.

Funding Notes

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Neuroscience or related area / subject.

This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

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