What role does the clusterin protein play in increasing Alzheimer’s risk?
Prof Paul Morgan
Cardiff University School of Medicine
1 October 2020 - 30 September 2023
Full project name:
Unravelling the molecular basis of the association of genetic variation in the clusterin gene with risk of Alzheimer's disease
Genetic differences in the clusterin gene have been linked to an increased risk of Alzheimer’s disease, this project will try to find the reason for this effect.
Scientists know that small changes to the genes that provide the instructions for a protein called clusterin lead to an increased risk of developing Alzheimer’s disease. The clusterin protein has also been found in amyloid plaques which build up in the brain during Alzheimer’s disease.
A PhD student in Prof Morgan’s lab will investigate if, and how, variations to the clusterin gene changes the amount of the protein in the brain. The first step towards their goal will be to find a reliable and accurate way to measure levels of clusterin in the blood, spinal fluid and brain.
Once they can measure clusterin levels, the student will be able to test the prediction that the changes to the genes affect the amount of the protein being made by cells in the brain. The researcher will work with biological data experts to look at individual genetic changes, but also investigate the effect of combinations of different genes.
The PhD student will also explore how clusterin is made and released from cells in the brain by using stem cells in a dish that have the variations of the DNA code known to increase Alzheimer’s risk. This will help to confirm that the effects are due to production of clusterin and understand which part of the production pathway the genes change.
A better understanding of this pathway will add detail to our understanding of how amyloid builds up in the brain during Alzheimer’s, and present a new avenue for future treatments.
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