Alzheimer's linked to new cholesterol-related gene variation

CHICAGO (AP) _ A variation in a gene that is supposed to help the brain break down cholesterol may play a role in some cases of Alzheimer's disease, researchers say. <br><br>A study found that people

Monday, January 20th 2003, 12:00 am

By: News On 6

CHICAGO (AP) _ A variation in a gene that is supposed to help the brain break down cholesterol may play a role in some cases of Alzheimer's disease, researchers say.

A study found that people with this variant form face double the risk of developing late-onset Alzheimer's, the most common form of the disease. It typically develops after age 65.

The gene, called CYP46, is involved in production of an enzyme that helps break down excess cholesterol in the brain. The research suggests that the variation might hamper production of the enzyme, resulting in a buildup in the brain of cholesterol and a gummy protein called beta amyloid.

The research, though preliminary, fits in with growing evidence that elevated cholesterol levels may raise the risk of Alzheimer's.

It also adds to evidence that genetics are involved. Late-onset Alzheimer's already has been linked to another genetic variation in a different gene involved in helping transport cholesterol throughout the body. That variation is called APOE-4.

In the new study, patients with both the CYP46 and APOE-4 variants were almost 10 times more likely to develop the mind-robbing disease than those with neither variation. They also had the highest brain levels of beta amyloid.

Autopsies also showed participants with just the CYP46 variant had significantly more beta amyloid deposits than those without the variant.

Dr. Andreas Papassotiropoulos at the University of Zurich and colleagues studied more than 400 European patients with or without Alzheimer's. The CYP46 variant was found in about 40 percent of participants.

The findings appear in January's Archives of Neurology.

Most of the estimated 4 million Americans with Alzheimer's have late-onset disease. It affects about one in 10 Americans over age 65 and nearly half of those over 85, according to the Alzheimer's Association.

An increasing number of studies suggest that cholesterol plays an important role in regulating beta amyloid.

Studies such as Papassotiropoulos' suggest that inhibiting cholesterol breakdown in the brain ``might represent a viable treatment'' for Alzheimer's, Dr. Benjamin Wolozin of Loyola University Medical Center in Maywood, Ill., said in an accompanying editorial.