New evidence that viruses may play a role in Alzheimer’s
WASHINGTON — Viruses that sneak into the brain just might play a role in Alzheimer’s, scientists reported Thursday in a provocative study that promises to re-ignite some long-debated theories about what triggers the mind-robbing disease.
The findings don’t prove viruses cause Alzheimer’s, nor do they suggest it’s contagious.
But a team led by researchers at New York’s Mount Sinai Health System found that certain viruses — including two extremely common herpes viruses — affect the behavior of genes involved in Alzheimer’s.
The idea that infections earlier in life might somehow set the stage for Alzheimer’s decades later has simmered at the edge of mainstream medicine for years. It’s been overshadowed by the prevailing theory that Alzheimer’s stems from sticky plaques that clog the brain.
Thursday’s study has even some specialists who never embraced the infection connection saying it’s time for a closer look, especially as attempts to block those so-called beta-amyloid plaques have failed.
“With an illness this terrible, we cannot afford to dismiss all scientific possibilities,” said Dr. John Morris, who directs the Alzheimer’s research center at Washington University School of Medicine in St. Louis. He wasn’t involved in the new research but called it impressive.
The study also fits with mounting evidence that how aggressively the brain’s immune system defends itself against viruses or other germs may be riskier than an actual infection, said Alzheimer’s specialist Dr. Rudolph Tanzi of Massachusetts General Hospital. With Harvard colleague Dr. Robert Moir, Tanzi has performed experiments showing that sticky beta-amyloid captures invading germs by engulfing them — and that’s why the plaque starts forming in the first place.
“The question remained, OK, in the Alzheimer brain what are the microbes that matter, what are the microbes that trigger the plaque?” explained Tanzi, who also had no role in the new research.
The team from Mount Sinai and Arizona State University came up with some viral suspects — by accident. The study, funded by the National Institutes of Health, wasn’t hunting viruses but was looking for new drug targets for Alzheimer’s. The researchers were using complex genetic data from hundreds of brains at several brain banks to compare differences between people who’d died with Alzheimer’s and the cognitively normal.
The first clues that viruses were around “came screaming out at us,” said Mount Sinai geneticist Joel Dudley, a senior author of the research published Thursday in the journal Neuron.
The team found viral genetic material at far higher levels in Alzheimer’s-affected brains than in normal ones. Most abundant were two human herpes viruses, known as HHV6a and HHV7, that infect most people during childhood, often with no symptoms, and then lie dormant in the body.
That wasn’t unusual. Since 1980, other researchers have linked a variety of bacteria and viruses, including another type of herpes that causes cold sores, to an increased risk of Alzheimer’s. But it was never clear if germs were merely bystanders, or actively spurring Alzheimer’s.
The new study went farther: Researchers used computer models to check how the viral genes interacted with human genes, proteins and amyloid buildup, almost like the viruses’ social media connections, Dudley explained.
“We’re able to see if viral genes are friending some of the host genes and if they tweet, who tweets back,” Dudley said.
They found a lot of interactions, suggesting the viruses could even switch on and off Alzheimer’s-related genes. To see if those interactions mattered, the researchers bred mice lacking one molecule that herpes seemed to deplete. Sure enough, the animals developed more of those amyloid plaques.
“I look at this paper and it makes me sit up and say, ‘Wow,’” said Alzheimer’s Association scientific programs director Keith Fargo.
He said the research makes a viral connection much more plausible but cautioned that the study won’t affect how today’s patients are treated.
If the findings pan out, they could change how scientists look for new ways to treat or prevent Alzheimer’s, said Dr. Miroslaw Mackiewicz of NIH’s National Institute on Aging. Already, NIH is funding a first-step study to see if an antiviral drug benefits people who have both mild Alzheimer’s and different herpes viruses.
CHICAGO — Now that the world’s leading public health group says too much Minecraft can be an addiction, could overindulging in chocolate, exercise, even sex, be next?
The short answer is probably not.
The new “gaming disorder” classification from the World Health Organization revives a debate in the medical community about whether behaviors can cause the same kind of addictive illness as drugs.
The strictest definition of addiction refers to a disease resulting from changes in brain chemistry caused by compulsive use of drugs or alcohol. The definition includes excessive use that damages health, relationships, jobs and other parts of normal life. Brain research supports that definition, and some imaging studies have suggested that excessive gaming might affect the brain in similar ways.
Under a looser definition, addiction is considered “a disease of extreme behavior. Any behavior carried to extreme that consumes you and keeps you from doing what you should be doing becomes an addiction as far as life is concerned,” said Dr. Walter Ling, a UCLA psychiatrist.
In its widely used manual for diagnosing mental illness, the American Psychiatric Association calls excessive video gaming a “condition” but not a formal diagnosis or disease, and says more research is needed to determine if it qualifies as an addiction.
DRUGS AND THE BRAIN
Certain drugs including opioids and alcohol can over-activate the brain’s reward circuit. That’s the system that under normal circumstances is activated when people engage in “behaviors conducive to survival” including eating and drinking water when thirsty, explained Dr. Andrew Saxon, chairman of the association’s addiction psychiatry council. The brain chemical dopamine regulates these behaviors, but narcotic drugs can flood the brain with dopamine, encouraging repeated use and making drug use more rewarding that healthy behaviors, Saxon said. Eventually increasing amounts are needed to get the same effect, and brain changes lead to an inability to control use.
WHAT ABOUT OTHER SUBSTANCES?
Caffeine is a stimulant and also activates the brain’s reward system, but to a much lesser degree than addictive drugs. The “reward” can make people feel more alert, and frequent users can develop mild withdrawal symptoms when they stop, including headaches and tiredness. Caffeine-containing chocolate may produce similar effects. Neither substance causes the kinds of life problems found in drug addiction, although some coffee drinkers develop a tolerance to caffeine and need to drink more to get the same “buzz” or sense of alertness.
The World Health Organization recognizes caffeine “dependence” as a disorder; the American Psychiatric Association does not and says more research is needed.
“The term ‘addiction’ is tossed around pretty commonly, like ‘chocoholic’ or saying you’re addicted to reality TV,” said Dr. Ellen Selkie, a University of Michigan physician who studies teens’ use of digital technology. But addiction means an inability to control use “to the point where you’re failing at life,” she said.
WHAT ABOUT BEHAVIOR?
The only behavior classified as an addiction in the American Psychiatric Association’s diagnostic manual is compulsive gambling. To be diagnosed, gamblers must have several symptoms including repeatedly gambling increasing amounts of money, lying to hide gambling activity, feeling irritable or restless when trying to stop, and losing jobs or relationships because of gambling. Research suggests excessive gambling can affect the brain in ways similar to addictive drugs. Since the diagnostic manual was last updated, in 2013, studies have bolstered evidence that excessive video gaming may do the same thing, and some experts speculate that it may be added to the next update.
The manual doesn’t include sex addiction because there’s little evidence that compulsive sexual behavior has similar effects on the brain.
Many excessive gamblers, gamers and sex “addicts” have other psychiatric conditions, including anxiety, attention deficit disorder and depression, and some mental health specialists believe their compulsive behaviors are merely symptoms of those diseases rather than separate addictions.
Excessive use of the internet and smartphones is also absent from the psychiatric manual and World Health Organization’s update. Psychiatrists disagree on whether that is a true addiction — partly because overuse is hard to measure when so many people need to use their smartphones and the internet for their jobs.
DOES THE TERM MATTER?
The World Health Organization’s decision to classify excessive video gaming as an addiction means “gaming disorder” will be added to this year’s update to the organization’s International Classification of Diseases. Doctors worldwide use that document to diagnose physical and mental illnesses. Insurers, including Medicaid and Medicare, use billing codes listed there to make coverage decisions. The American Psychiatric Association’s manual is widely used for defining and diagnosing mental disorders. If conditions aren’t listed in these documents, insurance coverage for treatment is unlikely.