U.S. National Institute on Aging/via Wikimedia Commons
A PET scan of the brain of a person with Alzheimer's disease.
A PET scan of the brain of a person with Alzheimer's disease. U.S. National Institute on Aging/via Wikimedia Commons
Finally, there's some good news about Alzheimer's disease.
It turns out that a few lucky people carry a genetic mutation that greatly reduces their risk of getting the disease, an Icelandic team reports in the journal Nature.
The mutation also seems to protect people who don't have Alzheimer's disease from the cognitive decline that typically occurs with age.
The mutation is very rare, but its discovery is generating fresh optimism about experimental drugs that act on the same system in the brain.
"I'm very excited by it," says Robert Vassar of Northwestern University, who has spent much of his career studying the process that causes plaques to form in the brains of people with Alzheimer's.
Those plaques are made of a substance called amyloid beta. The mutation discovered by the Icelandic researchers alters a gene that affects production of amyloid beta.
A study of the genomes of about 1,800 Icelanders found that the mutation "confers a very, very strong protection against the disease," says Kari Stefansson, a geneticist at deCODE genetics in Reykjavik and one of the study's authors.
People who had the mutation produced about 40 percent less of the proteins that become amyloid beta plaques, Stefansson says.
Previous genetic studies had found only mutations that increased a person's chance of getting Alzheimer's because they increased production of amyloid beta.
"This current mutation actually reduces amyloid beta production," Vassar says, "and it's protective for Alzheimer's disease."
One reason scientists are excited by the discovery is because of the way the mutation works, he says.
In order to form amyloid beta, the brain has to first cut up a larger molecule. It does this using an enzyme called BACE1.
"BACE 1 is like a pair of molecular scissors and what the mutation does is sort of interfere with the way the molecular scissors can cut," Vassar says. "It sort of dulls the blades."
That's exactly what drug companies are trying to do with experimental drugs known as BACE1 inhibitors. Several of these drugs are now being tried in people, although definitive results are probably years off.
If the experimental drugs do work against Alzheimer's, they might also help older people who don't have the disease, Stefansson says.
Ordinarily, people in their 70s, 80s and 90s have a slow but steady decline in memory and thinking, he says. But the Icelandic researchers found that this happened more slowly in people who carried the mutation.
The finding suggests amyloid beta is involved not only in Alzheimer's disease, Stefansson says, but also in the typical memory and thinking problems associated with aging.
The new study also makes it clear that amyloid beta is the key to finding a treatment for Alzheimer's, according to Rudolph Tanzi of Harvard Medical School and Massachusetts General Hospital, a researcher who helped discover the gene studied by the Icelandic team.
Tanzi says Alzheimer's researchers and drug companies need to attack amyloid beta with the same determination that heart disease experts began attacking cholesterol several decades ago.
"We've got to have that same focus with Alzheimer's disease, and I'm hoping that this paper will galvanize us to say, 'OK, this is our target,' " Tanzi says.
Most researchers agree. But some still think amyloid isn't the whole story. They point out that so far, no drug that targets amyloid has managed to slow down Alzheimer's.