January 12, 2010 – (BRONX, NY) – Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a "longevity gene" helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene's effect are now under development, the researchers note, and could help protect against Alzheimer's disease.
The paper describing the Einstein study is published in the January 13 edition of the Journal of the American Medical Association.
"Most work on the genetics of Alzheimer's disease has focused on factors that increase the danger," said Richard B. Lipton, M.D., the Lotti and Bernard Benson Faculty Scholar in Alzheimer's Disease and professor and vice chair in the Saul R. Korey Department of Neurology at Einstein and senior author of the paper. As an example, he cites APOE ε4, a gene variant involved in cholesterol metabolism that is known to increase the risk of Alzheimer's among those who carry it.
"We reversed this approach," says Dr. Lipton, "and instead focused on a genetic factor that protects against age-related illnesses, including both memory decline and Alzheimer's disease."
In a 2003 study, Dr. Lipton and his colleagues identified the cholesteryl ester transfer protein (CETP) gene variant as a "longevity gene" in a population of Ashkenazi Jews. The favorable CETP gene variant increases blood levels of high-density lipoprotein (HDL) – the so-called good cholesterol – and also results in larger-than-average HDL and low-density lipoprotein (LDL) particles.
The researchers of the current study hypothesized that the CETP longevity gene might also be associated with less cognitive decline as people grow older. To find out, they examined data from 523 participants from the Einstein Aging Study, an ongoing federally funded project that has followed a racially and ethnically diverse population of elderly Bronx residents for 25 years.
At the beginning of the study, the 523 participants – all of them 70 or over – were cognitively healthy, and their blood samples were analyzed to determine which CETP gene variant they carried. They were then followed for an average of four years and tested annually to assess their rates of cognitive decline, the incidence of Alzheimer's disease and other changes.
"We found that people with two copies of the longevity variant of CETP had slower memory decline and a lower risk for developing dementia and Alzheimer's disease," says Amy E. Sanders, M.D., assistant professor in the Saul R. Korey Department of Neurology at Einstein and lead author of the paper. "More specifically, those participants who carried two copies of the favorable CETP variant had a 70 percent reduction in their risk for developing Alzheimer's disease compared with participants who carried no copies of this gene variant."
The favorable gene variant alters CETP so that the protein functions less well than usual. Dr. Lipton notes that drugs are now being developed that duplicate this effect on the CETP protein. "These agents should be tested for their ability to promote successful aging and prevent Alzheimer's disease," he recommends.
Other co-authors of the paper, "Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene with Memory Decline and Incidence of Dementia," are Cuiling Wang, Ph.D., Mindy Katz, M.P.H., Carol A. Derby, Ph.D., and Nir Barzilai, M.D., from Einstein, and Laurie Ozelius, Ph.D., from Mt. Sinai School of Medicine.
The research was funded by the National Institute on Aging, one of the 27 institutes and centers of the National Institutes of Health.
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is home to 2,775 faculty members, 625 M.D. students, 225 Ph.D. students, 125 students in the combined M.D./Ph.D. program, and 380 postdoctoral research fellows. In 2008, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving eight hospitals and medical centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.einstein.yu.edu
Journal of the American Medical Association