Genetic factors contribute to Alzheimer's disease that appears after age 80 years, but at least half of the susceptibility can be attributed to factors other than genes, according to a study published December 15th in the on-line edition of Annals of Neurology. The report comes from a Swedish twin study, the first to look specifically at the relative contributions of genes and the environment in the very old.

It is clear that mutations play a major role in Alzheimer's disease that develops in middle-aged people or elderly patients younger than 80 years. The current study is part of an ongoing effort to establish the role of genetic factors in Alzheimer's that appears in those in people in their eighties and nineties.

Researchers typically divide Alzheimer's into early-onset or late-onset forms, depending on whether the disease is diagnosed before or after age 65 years. Early-onset disease accounts for a minority of cases, and most of these are more common in certain families, suggesting a strong genetic component. Genetic research in families with inherited Alzheimer's disease has led to identification of several mutations that can cause early-onset disease.

However, for the larger group of late-onset patients, individual genes do not appear to be at fault. Researchers feel it is more likely that normal variations in sequence of many genes combine with the environment to cause the disease. Environment in this context is a broad category that includes everything from viruses and bacteria to diet, toxins, educational achievement, or life events--and environmental factors begin at conception.

Studying twins is valuable way to assess the genetic component of a disease. "Because we know that identical twins share all their genes in common and fraternal twins have one half their genes in common, we can use this information to quantify how important genes are," said lead author Nancy Pedersen, Ph.D.
"The added advantage of twins is that they are the same age, and we don't have problems with waiting until other family members have passed the age at risk for the disease," added Pedersen.

Several earlier twin studies suggested that even among late-onset cases of Alzheimer's disease, the contribution of genes was higher than that of the environment, perhaps as high as 75 percent. But these studies were not set up to specifically look at very old subjects. In the current study, Swedish researchers studied 662 pairs of twins between the ages of 52 and 98 years.

During the 5 years, on average, of follow-up, 5.8 percent of study participants were diagnosed with Alzheimer's disease, a figure consistent with other research.

Of the identical twin pairs where 1 sibling developed Alzheimer's disease, the other twin also developed the disease in 32.2 percent of cases. Among fraternal twins, this figure was only 8.7 percent. With use of statistical modeling techniques, the researchers were able to estimate that half or more of the susceptibility to Alzheimer's disease in later life is attributable to environmental causes.