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See Inside March 2010

Mutant Cholesterol Fends Off Dementia




Ursula Markus Photo Researchers, Inc.

Cholesterol may conjure up associations of cardiovascular disease, but growing evidence shows that the lipid has great importance in the health of the brain, where one quarter of the body’s cholesterol resides. A new study has found that a common alteration to a gene that controls the size of cholesterol particles slows a person’s rate of dementia and protects against Alzheimer’s disease.

Individuals with the mutation—a swap of one amino acid (isoleucine) for another (valine) in the gene for cholesterol ester transfer protein (CETP)—had “significantly slower memory decline,” report researchers in a paper published online January 12 in the Journal of the American Medical Association. In fact, those who harbored two valine alleles experienced cognitive decline 51 percent more slowly than those with isoleucine—and had a 70 percent reduction in their risk for developing Alzheimer’s.

The results are preliminary, and the precise dynamic behind this cognitively protective phenomenon remains unknown. But the gene has previously been linked to longevity, and work is already under way to design drugs that alter CETP function in the interest of helping those with heart disease, notes senior author Richard B. Lipton of the Albert Einstein College of Medicine. Those therapies, Lipton hopes, might also provide some of the cognitive benefits revealed in this study.

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