Largest ever genetic study of Alzheimer's reveals new disease genes
9 September 2009
The study, an international collaboration led by scientists at Cardiff University and part-funded by a £1.3 million award from the Wellcome Trust, scanned the entire genomes of 16 000 people in search of genes that predispose people to or protect them from developing Alzheimer's disease.
Previously just one gene, APOE4, was known to be associated with the most common form of the disease (though several others have been found for rarer forms).
The two new genes, CLU and PICALM, are the first to be discovered since 1993. A third gene has been identified by a separate study, with both papers published in the journal 'Nature Genetics'.
The CLU gene produces a protein called clusterin, which has a protective effect on the brain. In particular, it is thought to help clear amyloid plaques, which appear to contribute to Alzheimer's disease. Variation in the CLU gene could reduce this protection, leading to the development of Alzheimer's disease.
The PICALM protein is a key component of synapses, the connecting structures between nerve cells. It helps transport molecules into and within nerve cells, aiding the formation of memories, among other brain functions.
"We know that the health of synapses is closely related to memory performance in Alzheimer's disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development," said Professor Julie Williams from Cardiff University, a lead author on the paper.
"This research is changing our understanding of what causes the common form of Alzheimer's disease and provides valuable new leads in the race to find treatments and possibly cures."
Using the same method, the researchers are now planning a larger study involving 60 000 people for next year, which they hope will uncover other Alzheimer's disease genes.
A separate study, led by a team from France, identified another gene linked to Alzheimer's disease, CR1. Like CLU, the product of this gene is thought to be involved in clearing amyloid plaques.
Image: Digital artwork representing the problems of Alzheimer's disease. Credit: Adrian Cousins, Wellcome Images
References
Harold D et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 2009 [Epub ahead of print].
Lambert JC et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 2009 [Epub ahead of print].