In what promises to be a major breakthrough in our understanding of Alzheimer's disease, an international group of scientists has discovered 11 previously unknown genes that increase people's risk of developing this most common cause of dementia.
The study, undertaken by the International Genomics Project (IGAP) and co-led by Cardiff University, Wales, UK, is published online this week in Nature Genetics.
The large group of four teams comes from 145 academic centers around the world and comprises most of the world's experts in the genetics of Alzheimer's.
They believe the discovery, which now brings the total number of genes known to raise the risk of developing Alzheimer's disease to 21, will open new avenues of research to improve our knowledge about the mechanisms that underpin the brain-wasting disease.
Prof. Julie Williams, head of neurodegeneration at Cardiff School of Medicine's Medical Research Council (MRC) Centre on Neuropsychiatric Genetics and Genomics, led one of the four international teams. She says:
"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."
The study builds on genome-wide association analysis work that, since 2009, has found the other 10 genes already known to be linked with Alzheimer's.
Prof. Williams, who is also chief scientific advisor for Wales, says the biggest surprise was finding out that several of the new genes involve the body's immune response in causing dementia.
However, she cautions that although we now have details of 21 genes known to increase risk of developing Alzheimer's, "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," she adds.
Discovery 'confirms' immune system's involvement
For the study, the teams gathered genome data from 74,076 people from 15 countries around the world to find the 11 new genes.
The researchers say one of the most significant findings relates to the HLA-DRB5/DRB1 major histocompatibility complex region of the genome. This discovery confirms that the immune system is somehow involved in the disease. This same region is associated with multiple sclerosis and Parkinson's disease.
The discoveries revolve around the most common, late-onset type of Alzheimer's.
Prof. Williams says they now want to turn their attention to people with the early-onset form of Alzheimer's, who get a more severe form of the disease in their 40s and 50s:
"Their genetic architecture may hold the key to finding yet more genes involved in Alzheimer's. 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."
She says they will also be bringing together what has been found out about environmental factors that increase and decrease the risk of developing Alzheimer's disease.
Prof. Williams says these discoveries are greatly helped by the fact experts in the genetics of Alzheimer's set aside their urge to compete and instead come together in the large teams that are necessary to make these kinds of breakthroughs. Now the same needs to happen with the biologists, she adds:
"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."
The research was partly funded by the Medical Research Council, the Welsh Government and Alzheimer's Research UK.