Genetic factors important in development and timing of Alzheimer's disease

In a large study of twins, Alzheimer's disease appears to be highly heritable and genetic factors may also influence timing of the disease, according to an article in the February Archives of General Psychiatry, one of the JAMA/Archives journals.

Two-thirds of adults aged 65 years and older with dementia have Alzheimer's disease (AD), and the number of AD cases is predicted to increase with the growing older adult population. Although genetic risk factors for AD have been identified, only a fraction of AD cases can be explained by specific gene mutations. Studies of twins have been helpful in investigating the relative importance of genetic and environmental influences in disease development. For example, if identical (monozygotic) twins do not both have a disease, environmental factors may be implicated for its occurrence.

Margaret Gatz, Ph.D., University of Southern California, Los Angeles, and colleagues evaluated 11,884 pairs of twins from the Swedish Twin Registry to examine the association between genetic and environmental influences and AD. The study included patients from the registry who tested positive for dementia and their twins, plus a sample of twins without dementia. The researchers identified 392 pairs of twins in which one or both had AD.

The researchers estimated heritability for AD to be between 58 and 79 percent. Among pairs where both twins had AD, there was an average of 3.66 years difference in age at onset between 25 sets of identical twins, and 8.12 years difference between 20 sets of fraternal (dizygotic) twins. This lead the researchers to conclude that genes had a role in disease timing "…because age at onset of AD is significantly more similar for concordant [occurring in both twins] monozygotic pairs compared with concordant dizygotic pairs." Concordance rates were higher in women, reflecting their greater longevity.

"In the largest twin study to date, we confirmed that heritability for AD is high and that the same genetic factors are influential for both men and women," the authors write. "However, nongenetic risk factors also play an important role and might be the focus for interventions to reduce disease risk or delay disease onset."

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(Arch Gen Psychiatry. 2006; 63: 168-174. Available pre-embargo to media at www.jamamedia.org.)

Editor's Note: This work was supported by a grant from the National Institute on Aging, Bethesda, Md. Dr. Gatz held a Zenith Award from the Alzheimer's Association, Chicago.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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