A study by scientists at the University of Southampton has revealed new clues to why people who carry the Alzheimerâ€™s risk gene APOE4 may be more likely to develop the disease. The findings, which link the risk gene to clearance of the hallmark Alzheimerâ€™s protein amyloid, take scientists a step further towards understanding the devastating disease. TheÂ research, published on 25 July in the journal PLoS ONE, was funded by Alzheimerâ€™s Research UK.
The APOE gene is the biggest known genetic risk factor for late-onset Alzheimerâ€™s disease. People who carry the APOE4 version of the gene have a higher risk of developing the disease at an earlier age than people who carry APOE3 or APOE2. However, the reason for this increased risk has remained unclear.
One of the key features of Alzheimerâ€™s disease is the build-up of a toxic protein called amyloid in the brain. Higher levels of amyloid have been reported in blood vessels in the brains of people with APOE4, causing a condition called cerebral amyloid angiopathy (CAA). It is thought that CAA may contribute to Alzheimerâ€™s and the Southampton team, who specialise in studying blood vessels in the brain, set out to investigate this link further.
To examine the effect of the risk gene in the brain, the scientists used normal mice and mice bred to have human versions of either APOE4 or its neutral equivalent APOE3. They looked at the levels of amyloid in the blood vessels of these mice using a fluorescently labelled version of the protein that they could track.
Dr Cheryl Hawkes, an author on the study, said:
â€œWe found that only the mice with APOE4 had high levels of amyloid in the blood vessels of their brain, suggesting that people with the risk gene may not be able to clear the toxic protein as effectively from their brain. After delving a little deeper, we discovered that the blood vessels in mice with APOE4 were very different â€“ they were made up of a different set of components that may not work as well to clear amyloid.
â€œThese initial results are really exciting because they help us to build a bigger picture of the factors influencing a personâ€™s risk of Alzheimerâ€™s. The next step will be to move this study from mice into humans to confirm that we see a similar change.â€
Dr Simon Ridley, Head of Research at Alzheimerâ€™s Research, said:
â€œOur understanding of the factors that make up a personâ€™s risk of Alzheimerâ€™s is improving at an incredible rate. Across our lifestyle and the environment, our age, diet and our genes, the answers to what predisposes us to Alzheimerâ€™s are being found. Research like this makes the risk picture more complete, and moves us closer to developing new treatments and preventions that can avert this devastating disease.
â€œThere are around half a million people in the UK living with Alzheimerâ€™s disease, yet research into dementia remains hugely underfunded compared to other common diseases. If we are to make a real different to the lives of people with this devastating disease, we must continue to invest in research.â€
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