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Largest ever Alzheimer’s gene study unveils dementia mysteries

British scientists have discovered two new genes associated with Alzheimer’s disease, while French colleagues uncovered a third.

The results, from the largest ever Alzheimer’s genome-wide association study (GWAS) involving 16,000 individuals, are published in Nature Genetics. They are the first new genes found to be associated with the common form of Alzheimer’s disease since 1993.

The Alzheimer’s Research Trust spoke of “a leap forward for dementia research”, the MRC’s Sir Leszek Borysiewicz praised “a huge step towards achieving an earlier diagnosis of Alzheimer’s”, and the Welsh First Minister Rhodri Morgan hailed the Cardiff-led study as “a real feather in the cap of Welsh science”.

The study was funded by the Wellcome Trust, Medical Research Council, Alzheimer’s Research Trust and Welsh Assembly Government among others. The UK-led research involved scientists from universities in Cardiff, London, Cambridge, Nottingham, Southampton, Manchester, Oxford, Bristol and Belfast, who collaborated with Irish, German, Belgian, Greek and American institutions.

Previously only one gene, APOE4, had been associated with Alzheimer’s disease. This study reveals two further genes, CLU and PICALM, are related to the disease. This is expected to provide scientists with a much clearer route to developing new treatments.

The paper’s lead-author, Prof Julie Williams, Chief Scientific Adviser to the Alzheimer’s Research Trust, said: "Both CLU and PICALM highlight new pathways that lead to Alzheimer's disease. The CLU gene produces clusterin which normally acts to protect the brain in a variety of ways. Variation in this gene could remove this protection and contribute to Alzheimer's development. PICALM is important at synapses - connections between brain cells - and is involved in the transport of molecules into and inside of nerve cells, helping form memories and 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."

"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."

"It also shows that other genes can be identified using this method, and the group are already planning a larger study involving 60,000 people, which can be achieved within the next year."

Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, which part-funded the study, said: “These findings are a leap forward for dementia research. At a time when we are yet to find ways of halting this devastating condition, this development is likely to spark off numerous new ideas, collaborations and more in the race for a cure.

“The work of Professor Williams and colleagues shows how British researchers lead the world in the struggle to understand and defeat dementia. With the right support for scientists, we can offer hope to the 30 million people worldwide who live with dementia.

The First Minister for Wales, Rhodri Morgan, said: "This major breakthrough in the battle to understand and develop treatments for Alzheimer's is good news for the 37,000 people in Wales and their carers who are affected by Alzheimer's or other forms of dementia. It is a real feather in the cap of Welsh science that this important global study has been led by a Welsh scientist, Professor Julie Williams and that the Welsh Assembly Government was able to give financial support for her work. World-class research like this will help lead to improved treatment for this distressing disease, and may one day even mean we can cure dementia."

Sir Leszek Borysiewicz, Chief Executive of the Medical Research Council, said:

“Funding work on neurodegenerative diseases is a priority for us and MRC investment in this kind of innovative research is crucial in piecing together the Alzheimer’s puzzle. This study is a huge step towards achieving an earlier diagnosis of Alzheimer’s and improving the lives of the many people affected by the disease."

The team shared their data with a further French-led study, also published in Nature Genetics, which has revealed compelling evidence for a third gene associated with Alzheimer’s called CR1.

The only other genes that have been connected to Alzheimer’s disease are in extremely rare cases of familial Alzheimer’s disease, which is inherited in less than 1% of cases.

Andrew Scheuber | EurekAlert!
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