Genetic mutations that could account for more than one in five cases of Alzheimer’s disease have been found, in a significant leap forward for dementia research, scientists say.

British scientists have discovered two genes associated with the degenerative illness of the brain and their French colleagues uncovered a third. Having certain variations of the three genes could increase the risk of having “common” late-onset Alzheimer’s by ten to 15 per cent, the researchers say.

It is thought that cancelling out their effects could prevent almost 100,000 cases of Alzheimer’s disease in the UK each year.

The studies, published in the journal Nature Genetics, describe the first new genetic clues for dementia to be identified since 1993, when a mutant form of a gene called APOE was found to account for about a quarter of cases. A reliable genetic screening test for Alzheimer’s is unlikely to be available for many years but the discovery of further genetic links pave the way for possible new treatments. On the basis of further research, existing drugs such as aspirin or ibuprofen may also slow the pace of mental decline.

Alzheimer’s is the most common form of dementia, affecting an estimated 400,000 people in Britain. This number is expected to grow to nearly a million within 20 years.

The British-led study was the largest genetic investigation of Alzheimer’s ever conducted. The scientists examined half a million variations in the genetic codes of 4,000 people with Alzheimer’s disease and 8,000 healthy people, looking for any differences that could be associated with the condition. They found that common non-protective versions of genes known as clusterin (CLU) and PICALM might account for 19 per cent of disease cases.

The French-led study, which looked at more than 14,000 DNA samples, also highlighted clusterin as well as complement receptor 1 (CR1), mutations of which could account for a further four per cent of cases.

Professor Julie Williams, who led the British-based study at the University of Cardiff, described the research as “the biggest advance in Alzheimer’s research in 15 years”.She added: “If we were able to remove the detrimental effects of these genes through treatments, we could reduce the proportion of people developing Alzheimer’s by 20 per cent. In the UK alone this would prevent just under 100,000 people developing the disease.”

Clusterin is known to protect the brain in a number of ways. Like APOE, it helps rid the brain of potentially destructive amyloid protein. But it also dampens down damaging inflammation caused by an overactive immune response — a function it shares with CR1.

Previously inflammation seen in the brains of Alzheimer’s sufferers was thought to be a secondary effect of the disease, caused by the build-up of plaques of amyloid protein that can have a devastating effect on memory and behaviour. The new findings suggested, however, that it might actually be a primary cause, raising the possibility of fighting Alzheimer’s with common anti-inflammatory drugs such as aspirin and ibuprofen.

Professor Williams said that a number of drug companies had already shown interest in the research, which was funded by the Wellcome Trust, Medical Research Council and Alzheimer’s charities.

The Cardiff researchers are now planning an even larger study, involving up to 60,000 people, to provide more evidence of the genetic causes of Alzheimer’s, which are thought to account for between 60 per cent and 80 per cent of a person’s risk of developing the disease.

Rebecca Wood, chief executive of the Alzheimer’s Research Trust, said: “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.”

Susanne Sorensen, head of research at the Alzheimer’s Society charity, added: “These discoveries will enable scientists to follow new avenues of investigation as they piece together the causes of Alzheimer’s disease — likely to be a mixture of genes, lifestyle and life events. Most importantly it could also lead to new drug treatments.”

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