"We know that it protects against disease in blood vessels," he said. "It lowers the risk of heart attack and stroke, and stroke is a risk factor for cognitive decline. So it protects the brain against atherosclerotic disease.
"The other mechanism is more speculative. It might protect against formation of proteins involved in Alzheimer's disease, such as beta-amyloid," Lipton said. The buildup of beta-amyloid protein plaques within brain tissue has long been a hallmark of Alzheimer's disease.
One expert found the study results intriguing.
"It's a great candidate gene for research on Alzheimer's disease and dementia," said Dr. James Burke, director of the Memory Disorders Clinic at Duke University Medical Center in Durham, N.C.
The benefit probably does not come from improved blood flow to the brain, he said. "I think it's related to lipid-cholesterol transport and metabolism," Burke said. Drugs that raise HDL level in the same way as the variant gene might therefore be useful against Alzheimer's disease, he reasoned.
According to the researchers, the CETP gene variant was first identified in a population of Ashkenazi Jews, descendents of western and central Europeans. The current study was done among an ethnically diverse population of people living in the Bronx who have been followed for 25 years.
It remains a small study that requires verification in broader research, Lipton said. "We have enrolled 600 additional people who we are following and we hope to enroll other groups," he noted.
Most studies of the genetics of Alzheimer's disease have concentrated on genes associated with increased risk, such as the ApoE-a4 gene, which also is involved in cholesterol metabolism, Lipton pointed out. "We hope that by understanding the genetics of the condition we can improve diagnosis or treatment or both," he said.
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