- The Washington Times - Tuesday, July 14, 2009

In what could be a repeat of their blockbuster gene discovery of 1993, scientists at Duke University Medical Center have identified a second gene linked to an increased risk of Alzheimer’s disease.

The gene not only appears to predict risk but also pegs the approximate age of onset for the degenerative brain disorder that afflicts 5.3 million Americans.

If the Duke team’s findings are replicated by scientists elsewhere, the discovery could open an additional avenue of research for drug development.

“We now have the ability to look at both [genes],” said Dr. Allen Roses, director of Duke’s Deane Drug Discovery Institute and lead author of the study. Findings were presented Sunday at the annual meeting of the International Conference on Alzheimer’s Disease, in Vienna, Austria.

The announcement was met with great interest - and caution - by other scientists.

Since Dr. Roses and a team of gene hunters at Duke identified the first genetic link to Alzheimer’s disease 16 years ago, many promising leads have fizzled under further analysis.

“I think this is really interesting, but it needs to be replicated,” said Margaret Pericak-Vance, a genetics researcher at Miami University who was a key member of the group at Duke that identified the original gene, known as APOE.

The gene had been the only one associated with late-onset Alzheimer’s disease, the most common form, which strikes people after age 65 and gradually robs them of memory, personality and function.

Dr. Roses agreed that additional confirmation is necessary. He said he welcomes other groups’ attempts to verify the findings. In addition, he is working to set up a large, international study that will gauge how well the new gene predicts Alzheimer’s disease in the general population, and test a potential drug for people whose genetic tests indicate they are at high risk of developing the illness.

“We would love to be able to start a study by late 2010,” Dr. Roses said.

The new genetic target is called TOMM40, and it has been a subject of interest for several years to geneticists exploring the hereditary nature of Alzheimer’s disease.

Dr. Roses’ group focused on TOMM40, and identified how it and APOE appear to interact and predispose people to getting sick.

Like cards dealt from a deck, certain combinations of the two genes and their variations have significance. An unfortunate draw increases the risk of disease, and of whether it will strike before age 80.

For APOE, there are four varieties of the gene. If a person is dealt an APOE4 gene from his mother and an APOE4 gene from his father, he has a double shot of APOE4 - the highest genetic risk for Alzheimer’s.

About half the cases of late-onset Alzheimer’s disease are associated with APOE4.

But the other half remained a mystery.

Now it turns out that the APOE3 version of the gene may also be important, depending on what’s simultaneously dealt from the TOMM40 deck.


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