Alzheimer's found to be mostly genetic 6/2/06. By the University of Southern California Largest twin study ever undertaken confirms highest estimates of genetic risk.

Alzheimer's disease has a genetic cause in up to 80 per cent of cases, according to a study of nearly 12 000 pairs of twins that appears in the February 2006 issue of Archives of General Psychiatry.

Past estimates of Alzheimer's risk varied widely, with the highest numbers sometimes greeted with scepticism.

"Our finding confirms the higher estimates that have been suggested previously. The important thing is that no one has had this large a sample before," said Margaret Gatz, Professor of Psychology at the University of Southern California, adding that the size was ten times that of any previous study.

The study raises doubts about the widely held view that Alzheimer's has two forms: the 'familial', with genetic roots, and the 'sporadic', with environmental causes.

"In essence what we're doing is taking the folks who would have formerly been called sporadic, and testing how important genetic influences are ... and we're finding genetic influences are tremendously important," Gatz said. "It does suggest that there is an underlying genetic basis."

She warned, "This doesn't mean that environment is not important. Environment may be relevant not only for whether but also for when one gets the disease. Also, you can't go from these results to any one individual."

Even identical twins, who share all their genes, differ in their vulnerability. The study found only a 45 per cent concordance rate for identical male pairs. This means that of all pairs where one twin has Alzheimer's, 55 per cent of the healthy twins either will never get the disease or will develop it later in life.

In her previous research with twins, Gatz identified possible preventive or delaying factors, such as a low incidence of inflammatory disease or a work environment with a high degree of human interaction.

The sample for the study consisted of all participants in the Swedish Twin Registry aged 65 or older in 1998 - the year the study began - for a total of 11 884 twin pairs.

Of these, 392 pairs showed evidence of Alzheimer's in at least one twin.

In the model that best fit the data, genetic influence accounted for 79 per cent of Alzheimer's risk, with 95 per cent confidence in a range of 67 to 88 per cent.

The other 21 per cent of Alzheimer's risk was due to non-shared environmental causes. Risk from shared environments, such as childhood settings that were the same for both twins, was statistically negligible.

Genetic risk for Alzheimer's was the same for men and women after controlling for age.

The international team who carried out the study were from Göteborg University, Jönköping University and Karolinska Institutet in Sweden, as well as from University of Southern California, the University of California at Riverside and the University of South Florida.

Adapted from a news release by the University of Southern California.

Further reading

Gatz M, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006 Feb;63(2):168-74. Abstract