Gene Linked to Late-Onset Alzheimer's Disease

A specific change in a gene may increase the risk of developing Alzheimer’s disease (search) late in life, according to a new study.

Researchers say the discovery could lead to a better understanding of Alzheimer’s disease and development of new ways to prevent and treat the disease.

Genetic mutations that increase the risk of Alzheimer’s have been found previously in four genes, three of which were linked to the rare and inherited form of Alzheimer’s that strikes earlier in life. The gene examined in this study, ubiquilin-1 (search), joins ApoE4 (search) as the second gene to be associated with an increased risk of the more common late-onset form of Alzheimer’s disease.

“We believe this variant moderately but significantly raises the risk of Alzheimer's disease," says researcher Lars Bertram, MD, of the Genetics and Aging Unit at the MassGeneral Institute for Neurodegenerative Disorders, in a news release.

Researchers say several additional genes my also increase the risk of developing Alzheimer’s and have not yet been identified.

New Gene Linked to Alzheimer’s Disease

In the study, which appears in the March 3 issue of The New England Journal of Medicine, researchers evaluated 19 different variations in ubiquilin-1 and two other genes -- located in the same region -- in a group of 437 families. The families had participated in a previous genetic screen of people with Alzheimer’s disease and their relatives. The researchers then compared these associations to a separate group of 217 sibling pairs.

The results showed that particular changes in the ubiquilin-1 gene were more common among people with Alzheimer’s than in their siblings who did not have the disease.

“The same variants of this gene conferred increased risk for Alzheimer's in both of these large study groups," says researcher Rudolph Tanzi, PhD, professor of neurology at Harvard Medical School, in the news release. "It was very encouraging to have the results confirmed in so many families."

Researchers also studied brain tissue from people with Alzheimer’s disease and healthy people to see if these genetic changes were associated with differences in the amount of the protein associated with ubiquilin-1. The protein is also called ubiquilin-1.

In both groups, the study showed that the same genetic changes that increased the risk of Alzheimer’s disease also led to increased production of a variant of the protein, and the overproduction was more pronounced in those with Alzheimer’s.

"Now we need to figure out what's wrong with too much ubiquilin-1 and with this different form," says Tanzi.

By Jennifer Warner, reviewed by Brunilda Nazario, MD

SOURCES: Bertram, L. The New England Journal of Medicine, March 3, 2005; vol 352: pp 884-894. News release, Massachusetts General Hospital.