Scientists reveal new clues to Alzheimer's risk gene

July 27, 2012, University of Southampton
Scientists reveal new clues to Alzheimer's risk gene
New clues into Alzheimer’s risk gene

(Medical Xpress) -- A study by scientists at the University of Southampton has revealed new clues to why people who carry the Alzheimer's risk gene APOE4 may be more likely to develop the disease.

The findings, which link the risk gene to clearance of the hallmark ’s protein amyloid, take scientists a step further towards understanding the devastating disease. The research, published on July 25 in the journal PLoS ONE, was funded by Alzheimer’s Research UK.

The APOE gene is the biggest known genetic risk factor for late-onset Alzheimer’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 Alzheimer’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 Alzheimer’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, from the University of Southampton, an author on the study, says: “We 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 in mice with were very different – they were made up of a different set of components that may not work as well to clear amyloid.

“These initial results are really exciting because they help us to build a bigger picture of the factors influencing a person’s risk of Alzheimer’s. The next step will be to move this study from mice into humans to confirm that we see a similar change.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research, said: “Our understanding of the factors that make up a person’s risk of Alzheimer’s is improving at an incredible rate. Across our lifestyle and the environment, our age, diet and our , the answers to what predisposes us to Alzheimer’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.

“There are around half a million people in the UK living with Alzheimer’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.”

Explore further: ApoE4 Alzheimer's gene causes brain's blood vessels to leak, die

Related Stories

ApoE4 Alzheimer's gene causes brain's blood vessels to leak, die

May 16, 2012
Common variants of the ApoE gene are strongly associated with the risk of developing late-onset Alzheimer's disease, but the gene's role in the disease has been unclear. Now, researchers funded by the National Institutes ...

Scientists find increased ApoE protein levels may promote Alzheimer's disease

April 3, 2012
Scientists at the Gladstone Institutes have enhanced our understanding of how a protein linked to Alzheimer's disease keeps young brains healthy, but can damage them later in life—suggesting new research avenues for ...

Recommended for you

Rocky start for Alzheimer's drug research in 2018

January 19, 2018
The year 2018, barely underway, has already dealt a series of disheartening blows to the quest for an Alzheimer's cure.

Alzheimer's disease: Neuronal loss very limited

January 17, 2018
Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. A joint ...

Anxiety: An early indicator of Alzheimer's disease?

January 12, 2018
A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of ...

One of the most promising drugs for Alzheimer's disease fails in clinical trials

January 11, 2018
To the roughly 400 clinical trials that have tested some experimental treatment for Alzheimer's disease and come up short, we can now add three more.

Different disease types associated with distinct amyloid-beta prion strains found in Alzheimer's patients

January 9, 2018
An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. In their paper published in Proceedings of the National ...

Advances in brain imaging settle debate over spread of key protein in Alzheimer's

January 5, 2018
Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer's disease - and hence that blocking its spread ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.