Duke cites landmark Alzheimer’s discovery

Confirmation is needed, but scientists report they found a 2nd gene for the brain disease, one that predicts age of onset.

By Sarah Avery
savery@newsobserver.com

Posted: Monday, Jul. 13, 2009

DURHAM 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 new 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 the study. Findings were presented Sunday at the 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 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. It generally hits people after the age of 65 and gradually robs them of memory, personality and function.

Roses agreed that additional confirmation is necessary. He said he welcomes other groups to verify the findings. He also 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, as well as test a potential drug for people whose genetic markers indicate they are at high risk of developing illness.

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

Roses’ group homed in on TOMM40 and identified how it and APOE appear to interact and predispose people to get 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 the risk of it striking before the age of 80.

There are four varieties of the APOE gene. If a person is dealt an APOE4 gene from his mother, and an APOE4 gene from his father, he’s got 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 a person has been simultaneously dealt from the TOMM40 deck.

In a way, TOMM40 is a wild card. It comes in two forms – long and short. If a long sequence of TOMM40 is found along with the APOE3 gene, a person has an increased risk of developing Alzheimer’s disease before age 80.

Roses estimates that TOMM40 may account for another 35 percent of Alzheimer’s cases.

“This is potentially a very exciting discovery,” said Dr. Daniel Kaufer of the UNC-Chapel Hill School of Medicine’s Memory and Cognitive Disorders Program. “There has been a big black hole in our knowledge of later onset Alzheimer’s. But the real clinical value remains to be seen down the road.”