Getting a ‘Clu’ about the causes of Alzheimer’s disease

Research project: Unravelling the molecular basis of the association of genetic variation in the clusterin gene with risk of Alzheimer’s disease.

Lead Investigator: Professor Paul Morgan

  • Institution: Cardiff University 
  • Grant type: PhD Studentship 
  • Duration: 36 months
  • Amount: £85,000.00

Project summary

Recent, huge multinational studies have identified different genes that play a role in the development of Alzheimer’s disease when changed or mutated. One such gene is called Clu and is the blueprint a human cell needs to make a protein called clusterin.

This project aims to understand how Clu is involved in the development of Alzheimer’s disease. By better understanding the different causes of dementia, we can develop better treatments in the future.

The background 

At present, the causes of Alzheimer’s disease are not fully understood, which makes it incredibly difficult to design new therapies and drugs to treat the disease.

Genetics is a powerful tool to help us understand the causes of different diseases and how they develop over time.

Recently, there have been several huge, multinational research collaborations to compare the genetic information of people living with Alzheimer’s disease with the genetics of those not living with the disease. These powerful studies help researchers spot which genes play important roles in Alzheimer’s disease and require further study. 

Clu is a gene that when changed or mutated is associated with increased risk of Alzheimer’s disease. It is the ‘blueprint’ a human cell needs to read in order to make a protein called clusterin which is found in the blood and spinal fluid.

However, from previous research studies there have been in inconsistent results about how the levels of clusterin in the blood and spinal fluid change in Alzheimer’s disease, or if the mutated Clu causes human cells to make more or less of the clusterin protein. 

What does this project involve? 

This PhD student will develop an accurate and very sensitive laboratory test that will be able to measure clusterin levels in human blood and spinal fluid samples consistently. They will then use this test to compare the levels of clusterin in the blood and spinal fluid of people living with Alzheimer’s disease and healthy individuals.

They will look at donated human brain tissue from a brain bank, to examine where clusterin is located in the human brain and compare healthy brains with those from people who lived with Alzheimer’s disease.

Finally, they will look at human brain cells grown in the lab, to understand how these cells make clusterin, and how a mutated Clu gene might change this process. 

How will this project help people with dementia? 

This project aims to fill an important gap in our knowledge about the genetics of Alzheimer’s disease. It will help us understand more about how our genes increase our risk of developing Alzheimer’s disease and more about what causes it. Understanding more about the causes of dementia is vital in helping us understand how to develop future treatments.

Finally, this research will create a valuable tool for the dementia research community which could be used by dementia researchers no matter where they are to understand more about what causes Alzheimer’s disease and how it affects the brain. 

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