(MRC DTP) The role of complement in the early stages of Alzheimer's Disease

Alzheimer’s disease (AD) has grown to be the leading cause of death in the UK, and yet it stands alone amongst the UKs biggest killers as having no disease-modifying treatment. Despite numerous clinical trials aimed at reducing the levels of insoluble and toxic amyloid protein in the brain – a key feature of AD – little progress has been made and new approaches are urgently required. We have recently completed a large screen of proteins in the human AD brain and shown that not only are multiple members of the complement pathway changing in their expression in AD, these changes appear to be seen early in the disease. Since complement activation in itself can prove toxic, and can further recruit damaging cellular immune responses, this represents a prime candidate for further study, with the eventual aim of targeting complement activation in the brain as a potential therapeutic approach. The overall aim of this project is therefore to validate complement activation as a key early event in human AD. This will be done by measuring the levels of key complement proteins by a range of tools, including immunofluorescence microscopy and mass spectrometry, not only in patients with confirmed AD but also in patients at risk of AD, or with early but asymptomatic disease, to determine at what stage in the disease process complement levels change. This will be correlated with other disease features such the presence of amyloid or immune cell activation. Since increased expression is not necessarily an indicator of increased activity, methods will also be developed to assess complement activation in tissue samples. Finally, this project will also assess complement activation (and the timing thereof) in an animal model of AD, providing critical data for future projects where inhibitors of complement activation, which we are developing for a different disease as part of a separate project, could potentially be repurposed for use to slow or prevent the progression of AD. 

ttps://www.research.manchester.ac.uk/portal/r.unwin.html https://www.research.manchester.ac.uk/portal/catherine.lawrence.html http://www.eyetuebingen.de/clarklab/ 

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

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