Scientists at Duke University Medical Center announced this morning they 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 confirmed by scientists elsewhere, it would mark the most significant hereditary marker for the disease since a Duke team identified the first Alzheimer's gene 16 years ago.
That gene, APOE, is associated with about 30 percent to 50 percent of late-onset Alzheimer's disease, the most common form that hits people after the age of 65 and gradually robs them of memory, personality and function.
"This is a bigger deal" than the APOE discovery, said Dr. Allen Roses, director of Duke's Deane Drug Discovery Institute and lead author of the study.
The findings were presented today at the annual meeting of the International Conference on Alzheimer's Disease in Vienna, Austria. Other scientist cautioned that the findings need to be independently verified.
“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.
Since the team at Duke identified the first genetic link to Alzheimer’s disease 16 years ago, many promising leads have fizzled under further analysis.
The new genetic target is called TOMM40, and it appears to interact with a variation of APOE to predispose people to getting sick. The APOE gene comes in four versions, and APOE4 is associated with the highest genetic risk for Alzheimer’s.
Now it turns out that the APOE3 version of the gene may also be important, depending on what’s simultaneously inherited in the TOMM40 gene.
TOMM40 comes in two forms — long and short. Roses' group showed that people who get a long sequence of TOMM40 along with the APOE3 gene have an increased risk of developing Alzheimer’s disease before the age of 80. Those who get a short version along with APOE3 are likely to have a later onset.
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, a neurologist and director 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.”
Kaufer and others noted that a gene discovery doesn’t necessarily result in new treatments.
Dr. Donald Schmechel, a neurologist who was on the APOE team at Duke and now runs a center to treat Alzheimer’s patients in Granite Falls, said identifying a second gene demonstrates the complexity of the disease, and the complexity of the challenge to treat it. “Finding the gene is not finding the cure,” Schmechel said. “The APOE discovery, in all honesty, was a fantastic insight, but no cure has emerged.”