Genes offer Alzheimer's breakthrough

A combination of two genes carried by one in 15 of the population is associated with a 30-fold increase in the risk of contracting Alzheimer's disease. Jeremy Laurance, Health Editor, considers the implications.

An advance in the understanding of one of the most feared diseases in the western world is reported by scientists today. Researchers at Oxford University have discovered a gene which interacts with a second, previously known gene to increase the risk of developing Alzheimer's disease.

People who carry both genes have 30 times the normal risk of developing the degenerative condition which strips the elderly of their dignity and affects an estimated 600,000 people in Britain. But the discovery raises questions about the ethics of testing for a disease that cannot be cured or prevented.

The Oxford discovery builds on earlier American research in 1993 which identified a variant of the Apo E gene on chromosome 19. People with the variant, known as E4 - about 25 per cent of the population - have a four- fold increased risk of developing Alzheimer's.

Now scientists at the Oxford project to investigate memory and ageing (Optima), headed by Professor David Smith, have discovered a variant of the gene for butrylcholinesterase, a protein, on chromosome 3, which interacts with Apo E4 to give a 30-fold increase in risk. When present alone, the variant of the gene, known as "K", increases the risk seven and a half times. Only those over 65 with late onset Alzheimers are affected. Although early onset Alzheimers is the same disease, it has a different cause.

Professor Smith, head of the department of pharmacology at Oxford University, said the findings were "very exciting" but had to be replicated before they could be relied on. "We were very surprised to find the interaction between the two genes. It suggests that the two proteins somehow interact to cause the disease. If it is replicated the discovery is important because it gives us a target to interrupt the disease process with drugs."

The findings are based on a study of 282 people over 65 in the Oxford area published in Human Molecular Genetics. Professor Smith said the discovery could open up a new chapter in Alzheimer's research but it raised "serious ethical questions" about testing. Bristol Myers Squibb, which funded the research, has applied to patent the test although it has no plans to develop one.

"I am 59 and I would not want to be tested. Even though if you have both gene variants you are at increased risk, it is not a certainty. Riding a motorbike is riskier than flying in an aeroplane but many people ride motorbikes and never have an accident."

The research team, which has been studying Alzheimers for 10 years, is now investigating the gene for a link with heart disease. Previous studies have shown the Apo E4 gene doubles the risk of heart disease.

Professor Smith said: "Is there an interaction [between the two gene variants] there too? If not then the effect is very specific to Alzheimer's, which would be a very important clue. If it does then it could be important in screening for heart disease."