January 12, 2010 / 10:30 PM / 9 years ago

Gene variant protects against Alzheimer's: study

CHICAGO (Reuters) - People with a gene linked to long life and good health are also less likely to develop Alzheimer’s disease, U.S. researchers said on Tuesday.

Alzheimer's disease patient Isidora Tomaz, 82, sits in her armchair with two chairs placed in front of her by her husband Amilcar Dos Santos (unseen) to prevent her from falling to the ground in their house in Lisbon September 15, 2009. REUTERS/Nacho Doce

They said people with two copies of a certain version of the cholesteryl ester transfer protein or CETP gene had significantly slower memory declines compared with people who had different versions of the gene.

“We’ve known for a long time that genetic factors matter in Alzheimer’s disease,” said Dr. Richard Lipton of Albert Einstein College of Medicine at Yeshiva University in New York, whose study appears in the Journal of the American Medical Association.

Lipton said most studies have sought to identify genetic variations that increase the risk of developing Alzheimer’s disease, such as APOE4.

“Instead, we looked for genes that protect against Alzheimer’s disease, and also for genes that might promote healthy brain aging,” Lipton said in a telephone interview.

An estimated 26 million people globally have Alzheimer’s disease, the most common form of dementia. The disease starts out with mild memory loss and confusion but escalates into complete memory loss and an inability to care for oneself.

Lipton’s team examined a variant of the CETP gene that is already associated with exceptional longevity and cardiovascular health.

They analyzed the DNA of more than 500 people who did not have dementia at the start of the study. The team also did annual memory tests.

After at least three years of follow up, 40 people developed dementia.

“We found in people who carry the longevity variant of CETP, there was a 70 percent reduction in the risk of Alzheimer’s disease, and the rate of annual decline on tests of memory was much lower,” Lipton said.

“That proved our hypothesis that at least this genetic variant associated with longevity was also associated with successful brain aging and protected against the onset of Alzheimer’s,” he said.

It is not exactly clear how this gene could protect the brain, but Lipton said people with the longevity variant of the CETP gene tend to have high levels of high density lipoprotein or HDL, the so-called “good” cholesterol that protects against heart disease.

“One possibility is the longevity gene promotes successful brain aging by preventing vascular disease,” he said.

Or, he said, the gene may have a direct protective effect against Alzheimer’s.

“Understanding the mechanism would allow you to discover drugs that mimic the genetic defect,” Lipton said.

Drug companies are already targeting the CETP gene in the hopes of raising levels of HDL or good cholesterol. Pfizer’s drug torcetrapib showed early promise, but the drug had excessive side effects, and Merck & Co now has a drug in late-stage clinical trials.

Despite decades of research, doctors still have few effective treatments for Alzheimer’s disease, which is expected to affect 100 million people by 2050.

Editing by Maggie Fox

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