The collaborative team of researchers was led by Margaret A. Pericak-Vance, PhD, Director of the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine; Joseph D. Buxbaum, PhD, Department of Psychiatry, Mount Sinai School of Medicine; and Jonathan L. Haines, PhD, Vanderbilt Center for Human Genetics Research, Vanderbilt University.
The researchers were able to identify small differences in the genetic sequences of the MTHFD1L gene in people with and without Alzheimer's disease. The team found that individuals with the variation may be nearly twice as likely to develop Alzheimer's disease as people without the variation. The researchers observed the gene variation throughout the human genomes of 2,269 people with late-onset Alzheimer's disease and 3,107 without the disease.
"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 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 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 Dr. Buxbaum. "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's disease. These findings will lead to a better understanding of what's happening in Alzheimer's disease, and how we can improve treatments," said Dr. Haines.
This work was supported by the National Institutes of Health National Institute on Aging (grants AG027944, AG20135, AG19757, AG010491, AG002219, and AG005138) and the National Institute of Neurological Disorders and Stroke (grants NS31153 and NS039764), 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 (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation's top 20 hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
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