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28th October 2013

Record number of Alzheimer's genes discovered in largest ever study

In a major new study, an international team of researchers has doubled the number of genes known to be involved in Alzheimer's disease from 10 to 21.

 

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This major breakthrough will significantly advance scientists’ knowledge of Alzheimer’s. It opens new research avenues and enables a better understanding of the disordered functional processes involved.

Published today in Nature Genetics and undertaken by the International Genomics Project (IGAP), the work details 11 new regions of the genome involved in the onset of this neurodegenerative condition. The research, part-funded by the UK's Medical Research Council, the Welsh Government and Alzheimer’s Research UK, builds on the genome-wide association analysis study that has since 2009 discovered 10 genes known to be associated with Alzheimer’s.

"This discovery will pinpoint new mechanisms underlying Alzheimer’s disease," said Professor Julie Williams, Head of Neurodegeneration at Cardiff University. "By combining the expertise and resources of geneticists across the globe, we have been able to overcome our natural competitive instincts to achieve a real breakthrough in identifying the genetic architecture that significantly contributes to our mapping of the disease.

"What surprised us most about the findings was the very strong pattern that showed several genes implicating the body’s immune response in causing dementia," she added. "We now have a total of 21 published genes known to increase the risk of developing Alzheimer’s, though a large portion of the genetic risk for the disease remains unexplained. Further research is still needed to locate the other genes involved before we can get a complete picture."

Since February 2011, the four largest international research consortiums on the genetics of Alzheimer’s have joined forces to accelerate the discovery of new genes. In less than three years, the IGAP scientists have been able to identify more susceptibility genes than was achieved in the previous 20 years.

Genetic data was collected from 74,000 individuals from 15 countries across the globe yielding 11 new gene discoveries. Among the most notable discoveries was found in the HLA-DRB5/DRB1 major histocompatibility complex region of the brain – confirming the involvement of the immune system in the disease. This same region is also associated with two other neurodegenerative disorders: multiple sclerosis and Parkinson’s disease.

Professor Williams commented on the direction the next phase of research will take:

"We will now turn our attention to people with early onset Alzheimer’s – people in their 40s and 50s afflicted with more severe forms of the condition. Their genetic architecture may hold the key to finding yet more genes involved. They carry a heavier genetic load than people who develop the condition in later life and will yield clues about what genetic markers we should be looking out for.

"We will also be compiling the findings of a series of major studies exploring the role environmental factors play in the development of Alzheimer’s, looking at what increases our risk and, conversely, what lessens it. These insights, we hope, will give people an opportunity to change their risk for the better, setting them on a safer course through life.

"Our work demonstrates that, given the complexity of such a disease, only a global collaboration will quickly find solutions to tackle this major threat. It would be greatly encouraging to also see the world’s molecular biologists all pulling together, breaking out of their silos and uniting in their aim of unraveling disease and developing the treatments to tackle it."

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:

"By mapping the genetics of the most common, late-onset form of Alzheimer’s, these findings highlight new biological processes that could significantly advance our understanding of this devastating disease. Alzheimer’s is a complex disease that requires a multi-faceted research approach and this important study shows the progress that can come through collaboration. Advances in technology have accelerated genetic research in recent years and Alzheimer’s Research UK is pleased to be supporting scientists at the cutting edge of this progress. While this new discovery holds real potential, the true value will come from pinpointing the exact genes involved, how they contribute to Alzheimer’s, and how this could be translated into benefits for people living with the disease."

The paper, entitled "Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease" is published in Nature Genetics.

 

 

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