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A genetic variation previously linked to longevity may also protect against the development of Alzheimer’s disease and other types of dementia, according to a new study. The variant affects cholesterol metabolism, boosting levels of high density lipoprotein (HDL), also known as “good” cholesterol, but it’s not yet clear how it could promote healthy aging in the brain. The new findings are likely to heighten interest in finding ways to chemically enhance good cholesterol–experimental drugs that mimic the molecular effects of the genetic variant are already in clinical tests for heart disease.

In a previous study of Ashkenazi Jews, researchers at Albert Einstein College of Medicine, in New York, found that a specific variation in a gene that codes for a protein called cholesteryl ester transfer protein (CETP) is more common in very long-lived people. Those older people who carried it also tended to have better cognitive function. (Ashkenazi Jews are often studied in genetic research because they originate from a relatively small founder population and possess less genetic complexity than other groups, making it easier to identify meaningful genetic targets.)

The new research, conducted by the same group on a more diverse sampling of people, found that those with two copies of the protective variant had a 70 percent lower chance of developing Alzheimer’s and other dementias, as well as a significantly lower rate of memory decline. “That’s a huge reduction,” says Richard Lipton, senior author of the study. “I’m not aware of other genetic factors that have that effect.” The research was published today in the Journal of the American Medical Association.

“It’s a striking reduction in the incidence of Alzheimer’s disease and dementia that they observe,” says Benjamin Wolozin, a neurologist at Boston University’s Alzheimer’s Disease Center, who was not directly involved in the research. “I think there is increasing evidence that factors that protect the cardiovascular system also protect against dementia.” Still, he cautions that other studies examining the same gene have had mixed results, so the findings are not yet conclusive.

The new findings are part of the Einstein Aging Study, an ongoing examination of a diverse group of people age 70 and older living in the Bronx. All were free of dementia when they enrolled in the study. Participants undergo regular cognitive testing, as well as annual medical and neurologic exams.

The frequency of the protective CETP variant in the general population is not well known. But Lipton says that his team’s previous studies have found that about 5 percent of 60-year-olds had it, and approximately 25 percent of centenarians–those age 100 or older. “It’s one of the more robust longevity genes we have identified,” says Lipton. The Einstein researchers are now trying to replicate the findings in another group. They also hope to find other genetic variants that protect against Alzheimer’s disease.

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Credit: Cecil H. Fox / Photo Researchers

Tagged: Biomedicine, brain, aging, Alzheimer's, longevity, dementia, cholesterol

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