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Five new Alzheimer’s disease genes uncovered

Discovery opens up prospect of preventive treatment

Caroline White

Monday, 04 April 2011

Five new genes that increase the likelihood of developing Alzheimer's disease have been discovered, bringing the total number of risk genes to 10 and providing a more accurate picture of the biological triggers of the disease.

The study, which involved a large international team of researchers, is published online in Nature Genetics.

It followed up previous work in 20,000 people with Alzheimer's disease and 40,000 healthy people, and confirms that Alzheimer's disease is a complex multifactorial condition.

The discovery has enabled the researchers to identify a series of patterns, which suggest that the immune and inflammatory responses of people with Alzheimer's disease differ from those of people who don’t develop it.

Several risk factors have now been implicated, including immune system response, the way in which the brain processes cholesterol and lipids, and for the first time, endocytosis —the removal of toxic amyloid beta protein from the brain.

“We now have four genes that implicate this very precise process [endocytosis], and it offers a very big clue that this process is playing a strong role in the development of Alzheimer's disease," commented lead author, Professor Julie Williams of Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.

She added: "What's exciting is the genes we now know of—the five new ones, plus those previously identified— are clustering in patterns."

In 2009, Professor Williams led the largest genetic investigation of Alzheimer's disease ever conducted, which involved analysing DNA from more than 16,000 people over two years.

"This study, plus our previous studies, means that we are beginning to piece together the pieces of the jigsaw and gain new understanding. We still have a long way to go, but the jigsaw is beginning to come together,” she said.

"If we were able to remove the detrimental effects of these genes through treatments, we hope we [could] help reduce the proportion of people developing Alzheimer's in the long-term."

Rebecca Wood, Chief Executive of Alzheimer's Research UK said: "UK scientists are leading the field in our understanding of the genetics of Alzheimer's. These findings are a step towards defeating dementia. We are yet to find ways of halting this devastating condition, but this work is likely to spark off new ideas, collaborations and more research.”

Professor Chris Kennard, Chairman of the MRC's Neuroscience and Mental Health Board, said: "Using genetics to understand individual predispositions to disease is a major strategic aim for the MRC. These are very exciting findings which, in the long term, we hope will lead to the development of treatments for this debilitating condition."

Dr John Williams, The Wellcome Trust's Head of Neuroscience and Mental Health added: "As our population ages, we will see more and more people affected by Alzheimer's disease. Understanding the complex processes that underpin the disease will be essential to earlier diagnosis and to developing improved treatments.”

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