A new approach to controlling blood cholesterol levels that is already being investigated to prevent cardiovascular disease also may be a potential treatment for Alzheimer's disease. In their report in the October 14 issue of Neuron, researchers from Massachusetts General Hospital (MGH) show that blocking a pathway that controls the distribution of cholesterol in cells dramatically reduces the number of amyloid plaques in the brains of transgenic mice. Some of the treated mice were much better at learning their way through a maze than were untreated mice.

"We found that this way of reducing cholesterol levels in the brains of living animals both decreased amyloid deposition and improved learning," says the study leader Dora Kovacs, PhD, director of the Neurobiology of Disease Laboratory in the Genetics and Aging Research Unit of MassGeneral Institute for Neurodegenerative Disorders. "As far as we know, this is the first study of cholesterol metabolism's impact on amyloid levels that included cognitive testing."

Researchers have been investigating a potential relationship between cholesterol metabolism and Alzheimer's since it was found that a particular variant of the gene for a protein called apoE significantly increased risk of the disease. Since the apoE protein transports cholesterol, that discovery suggested that disruption of cholesterol handling might cause or worsen the development of the amyloid plaques that characterize Alzheimer's disease. In addition, some epidemiologic studies have suggested that people taking statin drugs to control blood cholesterol have a reduced incidence of Alzheimer's.

In 2001 Kovacs' team showed in cells that the activity of an enzyme called ACAT, which controls whether cholesterol is stored in the cellular membrane or in intracellular droplets, also appears to regulate the formation of amyloid-beta, the protein fragments that make up amyloid plaques. The current study was designed to test tha
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
13-Oct-2004

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