U.S. researchers said they have discovered a gene variant that may help predict who is at risk to developing Alzheimer’s at a later stage and at what age will they begin to show symptoms of the condition.

The research team from the Duke University Medical Center uncovered the variants in the APOE gene that predispose carriers to Alzheimer’s disease. They said the TOMM40 gene may be the most highly predictive Alzheimer's gene discovered so far and could predict the age of Alzheimer's disease onset within a five- to seven-year window among people over 60.

Allen Roses, lead author of the study and director of the Deane Drug Discovery Institute at Duke University Medical Center said more than half the cases of Alzheimer’s are caused by the APOE gene and by adding Tomm40, the new genetic variation not only could they identify up to 85 % of inherited cases of Alzheimer’s disease, but they could pinpoint the onset of symptoms as well.

"If borne out through additional research, a doctor could evaluate a patient based on age, especially among those over age 60, their APOE genotype and their TOMM40 status, to calculate an estimated disease risk and age of onset," said Roses.

In the study the researchers conducted a detailed genetic screening on about 35 patients with Alzheimer’s disease, and analyzed their medical history from the time their symptoms started until death.

They found there despite Tomm40 and APOE genes being linked, there are key variations in the Tomm40 gene that are tied to Alzheimer’s disease development.

The APOE-4 gene already shown to predispose carriers to Alzheimer’s disease and the long version of Tomm40 which is the more dangerous form, and signals an earlier onset of Alzheimer’s disease, come together.

In the case of patients with another form, APOE-3 they can get either the long version or a short version and which one they get may help determine their Alzheimer’s history.

Elaborating on this, Roses said, if a person gets APOE-3 with the long version of Tomm40 from both their parents, they are likely to get Alzheimer’s disease by age 70. If they get one short form of Tomm40, the age of symptoms recedes to 78, and two short forms mean carriers may never develop Alzheimer’s, he said.                   

"It now looks fairly clear that there are two major genes -- APOE4 and TOMM40 -- and together they account for an estimated 85 to 90 percent of the genetic effect," Roses said.

The study was presented July 12 at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease, held in Vienna, Austria.

“As soon as people start forgetting things, they want to know if they will get Alzheimer’s disease,” Roses said. “That is what we are getting at. While this doesn’t say everyone will get Alzheimer’s disease at these ages, it is meaningful.”

Roses said additional studies are needed to confirm and build on the findings. The Duke team is planning a five-year study of APOE genotypes and TOMM40, along with a drug trial to assess prevention or delay of Alzheimer's disease onset.