Two common herpes viruses appear to play a role in Alzheimer's disease.
The viruses, best known for causing a distinctive skin rash in young children, are abundant in brain tissue from people with Alzheimer's, a team of scientists reports Thursday in Neuron. The team also found evidence that the viruses can interact with brain cells in ways that could accelerate the disease.
"Our hypothesis is that they put gas on the flame," says Joel Dudley, an author of the study and an associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mt. Sinai in New York City.
The finding adds credence to a decades-old idea that an infection can cause Alzheimer's disease. It also suggests that it may be possible to prevent or slow Alzheimer's using antiviral drugs, or drugs that modulate how immune cells in the brain respond to an infection.
But the study doesn't prove that herpes viruses are involved in Alzheimer's, says Dr. Richard Hodes, director of the National Institute on Aging, which helped fund the research.
"The data are very provocative, but fall short of showing a direct causal role," he says. "And if viral infections are playing a part, they are not the sole actor."
Even so, the study offers strong evidence that viral infections can influence the course of Alzheimer's, Hodes says.
Like a lot of scientific discoveries, this one was an accident. "Viruses were the last thing we were looking for," Dudley says.
He and a team of researchers were using genetic data to look for differences between healthy brain tissue and brain tissue from people who died with Alzheimer's.
The goal was to identify new targets for drugs. Instead, the team kept finding hints that brain tissue from Alzheimer's patients contained higher levels of viruses.
"When we started analyzing the differences, it just sort of came screaming out at us from the data," Dudley says.
The team found that levels of two human herpes viruses, HHV-6 and HHV-7, were up to twice as high in brain tissue from people with Alzheimer's. They confirmed the finding by analyzing data from a consortium of brain banks.
These herpes viruses are extremely common, and can cause a skin rash called roseola in young children. But the viruses also can get into the brain, where they may remain inactive for decades.
Once the researchers knew the viruses were associated with Alzheimer's they started trying to figure out how a virus could affect the course of a brain disease. That meant identifying interactions between the virus genes and other genes in brain cells.
"We mapped out the social network, if you will, of which genes the viruses are friends with and who they're talking to inside the brain," Dudley says. In essence, he says, they wanted to know: "If the viruses are tweeting, who's tweeting back?"
And what they found was that the herpes virus genes were interacting with genes known to increase a person's risk for Alzheimer's.
They also found that these Alzheimer's risk genes seem to make a person's brain more vulnerable to infection with the two herpes viruses.
But just having herpes virus present in the brain isn't enough to cause Alzheimer's, Dudley says. Something needs to activate the viruses, which causes them to begin replicating.
It's not clear what causes the activation, Dudley says, though he suspects some sort of change in the internal functions of brain cells.
Once the viruses do become active, they appear to influence things like the accumulation of the plaques and tangles in the brain associated with Alzheimer's. "They are sort of throwing a wrench in the works," he says.
The herpes viruses also seem to trigger an immune response in certain brain cells, Hodes says. These cells are part of an ancient immune system that has previously been implicated in Alzheimer's.
Most previous efforts to prevent or treat Alzheimer's have involved trying to reduce the plaques and tangles associated with the disease. Those efforts have failed to improve brain function even when they accomplished their immediate goal.
Those "distressing and disappointing failures" suggest it's time for some new approaches, Hodes says. And the new study suggests at least two.
One is to give antiviral drugs to people with high levels of herpes virus in their brains. The Institute on Aging is already funding a study to test this approach in people in the early stages of Alzheimer's, Hodes says.
Another approach is to prevent the brain's immune cells from reacting to the virus in ways that accelerate Alzheimer's, Hodes says. That's tricky, he says, because simply disabling the brain's immune cells could be harmful.
Even so, Hodes is optimistic.
"The more we learn about the disease process and the more targets we can address," he says, "the greater the probability we are going to slow or prevent the progression of Alzheimer's disease."
AUDIE CORNISH, HOST:
Researchers say two common viruses appear to play a role in Alzheimer's disease. NPR's Jon Hamilton reports on a finding that could lead to new strategies for preventing and treating Alzheimer's.
JON HAMILTON, BYLINE: Like a lot of scientific discoveries, this one was an accident.
JOEL DUDLEY: Viruses were the last thing we were looking for.
HAMILTON: Joel Dudley is an associate professor at the Icahn School of Medicine at Mount Sinai in New York. He's part of a team that compared healthy brain tissue with brain tissue from people who died with Alzheimer's. The goal was to identify new targets for drugs. Instead, Dudley says, they found that the brain tissue from Alzheimer's patients contained a lot more virus.
DUDLEY: When we started analyzing the differences, it just sort of came screaming out at us from the data alone.
HAMILTON: Levels of two human herpes viruses were up to twice as high in brain tissue from people with Alzheimer's. These viruses are carried by almost everyone and are best known for causing a skin rash in toddlers, but they can also get into the brain. The team confirmed the association with Alzheimer's using data on hundreds of brains from a consortium of brain banks. Then, Dudley says, they tried to figure out how these viruses could be affecting the course of a brain disease.
DUDLEY: We almost mapped out the social network, if you will, of which genes the viruses are friends with and who they're talking to inside the brain and if the viruses are tweeting, who's tweeting back.
HAMILTON: And Dudley says what they found was really intriguing.
DUDLEY: Actually, a lot of well-known Alzheimer's genes came up as either interacting with the virus genes or being influenced by them.
HAMILTON: It's not clear exactly how virus genes interact with Alzheimer's genes, but Dudley says it is clear that the same genes that make some brains more susceptible to Alzheimer's also seem to make them prone to infection with these herpes viruses. And once the viruses get inside brain cells, they can just sit there quietly for decades until something causes them to wake up. Dudley thinks that's when the trouble starts.
DUDLEY: These viruses are becoming activated, and then they put gas on the flame of the Alzheimer's pathology.
HAMILTON: In other words, they speed up the formation of the plaques and tangles associated with Alzheimer's. Richard Hodes directs the National Institute on Aging, which helped pay for the research. He says the finding is important but not conclusive.
RICHARD HODES: The data are very provocative but fall short of showing a direct causal role of viral infection.
HAMILTON: But he says the evidence is good enough to merit a study looking at whether antiviral drugs can delay or prevent Alzheimer's. So the Institute on Aging is funding a study that will test this approach. Hodes says the new research on viruses also hints at another way to fight Alzheimer's. These herpes viruses appear to trigger an immune response in the brain that can accelerate the disease. So Hodes says it might be possible to protect the brain with drugs that tweak the brain's immune system.
HODES: The more we learn about the disease process and the more targets we can address, the greater the probability is we are going to make the impact that so far has eluded us in slowing or preventing the progression of Alzheimer's disease.
HAMILTON: The new research appears in the journal Neuron. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.