Research Projects

How does occludin contribute to Alzheimer’s disease?

Awarded to:
Prof Stephen Wharton

Current award:

University of Sheffield

1 October 2020 - 30 June 2021

Full project name:

Occludin as a Mediator of Neuroglial RNA Dysmetabolism in Dementia






Alzheimer’s disease is the most common form of dementia accounting for two-thirds of all cases, around 500,000 people in the UK.

Occludin is a key molecule in brain blood vessels where it contributes to the blood brain barrier – a layer of protection that surrounds the brain. Now, scientists, including Prof Wharton from the University of Sheffield have found occludin in nerve cells and astrocytes - the star shaped support cells in the brain, and there is evidence that it acts unusually in Alzheimer’s disease.

Prof Wharton has reason to believe that occludin in nerve cells may be involved in regulating RNA, the biological messengers that carry instructions from the DNA code. Changes to occludin might alter these messages in damaged cells in dementia.

In a Pilot Project they will investigate how changes to occludin alter this message. They will use cells taken from the skin and reprogram them into nerve cells. They will genetically edit these cells, so that they no longer make the occludin protein. They will then determine how this affects the cells.

By carrying out this Pilot project, the team will also develop better methods to measure occludin in human brain tissue than have previously been possible.

Pilot projects like this are key for investigating early ideas, which have potential to lead onto larger projects.  This pilot study is needed to generate the key methods and reagents needed before proceeding to a more expensive major project.

We use a research technique where we take skin cells donated by people with Alzheimer’s disease and reprogram them into nerve cells that no longer produce occludin. This will allow us to reveal how this protein affects cells present in the brain. Finding out how occludin affects the brain may open the door to new ways to treat diseases like Alzheimer’s and we are pleased to see Alzheimer’s Research UK continue to back our research at this time.

Prof Stephen Wharton

Alzheimers research UK - Oxford - 250

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