New Alzheimer's Disease Gene Identified

Researchers Say Gene May Help Reveal People at Risk of Developing Alzheimer's

From the WebMD Archives

July 14, 2009 (Vienna, Austria) -- A newly identified gene may help predict who will develop Alzheimer's disease and the approximate age at which symptoms of the disorder will begin to appear.

The new gene, dubbed TOMM40, may be the most highly predictive gene discovered in Alzheimer's disease, according to lead researcher Allen Roses, MD, director of the Deane Drug Discovery Institute at Duke University Medical Center.

Roses should know; he discovered the variants in the ApoE gene that are associated with an increased risk for Alzheimer's disease.

The ApoE gene comes in one of three forms: ApoE2, ApoE3, and ApoE4. The ApoE4 variant is the most dangerous; it accounts genetically for 50% of late-onset cases of Alzheimer's disease. Adding in TOMM40 may help to pinpoint up to 90% of inherited cases of the disease, Roses says.

Perhaps more importantly, TOMM40 may help explain why many people with the most common version of the gene, ApoE3, also get the disease, Roses says. TOMM40 can also help predict the onset of symptoms within a five- to seven-year window among people over age 60, he tells WebMD.

The study was presented at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease.

New Alzheimer's Drugs Needed

If borne out through additional research, testing for the two genes could help doctors better calculate patients' estimated disease risk and age of onset, Roses says.

Having genes that can pinpoint who will develop Alzheimer's disease before symptoms develop will be beneficial once drugs to prevent or slow the course of the disorder become available, says William Thies, PhD, chief medical and scientific officer at the Alzheimer's Association.

"But right now, without a treatment to offer, it doesn't do the clinician much good to know who is at increased risk," he tells WebMD.

ApoE4 testing has been available for some time, and it's apparent that people do not want testing in the absence of treatment, Thies says. For now, testing is most useful for drug companies who want to enroll high-risk people in clinical trials, he says.

Currently, there are 5.3 million Americans living with Alzheimer's disease, which disrupts memory, learning, and other mental functions. By 2010, there will be nearly half a million new cases each year, and by 2050, there will be nearly a million new cases annually, according to the Alzheimer's Association.


Genetic Analysis

For the study, the researchers performed detailed genetic screening on 35 patients, looking at the area of DNA surrounding the ApoE gene.

They found that TOMM40 linked to ApoE3 in either short or long repeated sequences, while all ApoE4-linked repeated sequences were long.

Among people with the ApoE3 gene variant, those with the long version of TOMM40 develop Alzheimer's at an average age of 70, Roses reports. Those with the short version of TOMM40 and ApoE3 develop it at age 77.

ApoE4 always seems to be attached to the more dangerous, long version of TOMM40.

Thies says that a relatively small number of people were studied, and the findings need to be replicated in larger groups.

The Duke team is planning a larger study combined with a drug trial aimed at prevention or delay of disease onset.

WebMD Health News Reviewed by Louise Chang, MD on July 14, 2009



Alzheimer's Association 2009 International Conference on Alzheimer's Disease, Vienna, Austria, July 11-16, 2009.

Allen Roses, MD, director, Deane Drug Discovery Institute, Duke University Medical Center, Durham, N.C.

William Thies, PhD, chief medical and scientific officer, Alzheimer's Association, Chicago.

Alzheimer's Association web site: "Alzheimer's Facts and Figures."

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