The World Health Organization estimates that there are currently 18 million people worldwide with Alzheimer's disease, and this figure is projected to nearly double to 34 million by 2025. By looking at gene variation throughout the human genomes of 2,269 subjects with late-onset AD and 3,107 without the disease, researchers were able to pinpoint small differences in the genetic sequences of people with and without AD.

The study found that individuals with a particular variation in the gene MTHFD1L may be almost twice as likely to develop AD as those people without the variation.

"We are hopeful our identification of MTHFD1L as a risk gene for Alzheimer's disease will help us to better understand how this disease develops and potentially serve as a marker for people who may be at increased risk," said Adam Naj, Ph.D., post-doctoral fellow at the Hussman Institute and lead author of the study.

"Identifying this gene is important because the gene is known to be involved in influencing the body's levels of homocysteine, and high levels of homocysteine are a strong risk factor for late-onset Alzheimer's disease," said Dr. Pericak-Vance. "In addition, variations of the MTHFD1L gene have been reported to possibly increase the risk of coronary artery disease. Since the function of blood vessels in the brain may affect Alzheimer's disease, this finding may also help us understand how homocysteine levels and blood vessel function in the brain affect Alzheimer's disease."

"This finding gives us unique insight into possible interactions between genetic and environmental risk factors that contribute to AD," said Joseph Buxbaum, Ph.D., from Mount Sinai School of Medicine in New York and a senior author on the study. "We know of environmental and lifestyle factors that can impact homocysteine levels and it will be important to understand whether variations of the MTHFD1L gene can modulate these effects."

"By applying the new tools of genomics we are now making rapid progress in finding out what genetic changes are involved in Alzheimer disease. These findings will lead to a better understanding of what's happening in Alzheimer disease, and how we can improve treatments," said Jonathan Haines, Ph.D., principal investigator at Vanderbilt University School of Medicine.

This work was supported by the National Institutes of Health National Institute on Aging and the National Institute of Neurological Disorders and Stroke, the Alzheimer's Association, and the Louis D. Scientific Award of the Institut de France. Samples from the National Cell Repository for Alzheimer's Disease, which receives government support under a cooperative agreement grant awarded by the National Institute on Aging, were used in this study.