The News:

It has long been a controversial theory about Alzheimer’s disease (AD), often dismissed by experts as a random detour from mainstream research. But a new study by a team that includes prominent Alzheimer’s scientists who were previously skeptics of this theory may well change that.

The research offers compelling evidence for the idea that Viruses might be involved in Alzheimer’s, particularly two types of herpes that infect most people as infants and then lie dormant for years. The study, published last Thursday (June 28, 2018) in the journal Neuron, found that viruses interact with genes linked to Alzheimer’s and may play a role in how Alzheimer’s develops and progresses.

The authors emphasized they did not find that these viruses cause Alzheimer’s. But their research, along with another soon-to-be-published study, suggests that viruses could kick-start an immune response that might increase the accumulation of amyloid, a protein in human brains which clumps into the telltale plaques of Alzheimer’s.

“These viruses are probably significant players in driving the immune system in Alzheimer’s,” said Joel Dudley, the study’s senior author and an associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York. “I think they’re like gas on the flames of some pathology that may be immune-driven.”

“This definitely brings up the potential role of infection or infectious particles in the pathology of Alzheimer’s,” said Dr. John Morris, director of the Knight Alzheimer’s Disease Research Center at Washington University School of Medicine in St. Louis.

Dr. Morris, who was not involved in the research, said it provided the strongest evidence to date for a viral role.

The study analyzed samples from nearly 950 human brains in four different brain banks and found links to the genetic, molecular and clinical symptoms of Alzheimer’s.

“It’s a very complex disease, and the answer’s not going to be one thing,” Dr, Morris said. “If viruses are a part of that, we definitely need to take a look at it.”

Still, the new findings will be bolstered by another upcoming study in Neuron, led by Rudolph Tanzi and Robert Moir, neuroscientists at Massachusetts General Hospital and Harvard, who have broken ground on the virus idea for years.

Their new experiments, performed in mice and three-dimensional brain cells in a dish, found that the same herpes species ignited a protective reaction in amyloid, a protein present in all human brains. Dr. Tanzi describes this as “seeding” the amyloid, causing it to ensnare the virus in fibrous nets that form plaques. In this way, he said, viruses and other microbes are the “prequel” to the prevailing theory that Alzheimer’s is caused by amyloid accumulation the brain cannot clear out.

“It could lead to new therapeutic strategies down the road,” said Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute in Phoenix and one of several Alzheimer’s experts and longtime virus-theory skeptics who were co-authors on the study.

Steve’s Take:

For decades, herculean efforts have been made to cure, prevent, and/or forestall the ravages of Alzheimer’s but with nothing to show for the millions of hours of research and billions spent in labs and clinics.

That’s why whenever I read an article that apparently has found some small shard of new evidence about what may contribute to AD, I immediately take note. You see, an increasing number of my peers, age-wise at least, are now being struck down with dementia, which often morphs into full-blown AD later, before they finally succumb to it.

Albeit the above report sounds encouraging with its confirmation of the herpes-AD connection, I was struck by how quickly my own hope that some progress was actually made evaporated when I reached the end of it.

Merely finding herpes virus, it turns out, falls well short of demonstrating that it or other microbes cause Alzheimer’s. That idea has been batted around since at least the 1950s, STAT News points out, but has never overcome a key objection: degenerating brains might just be more inviting to pathogens than healthy brains. In that case, the pathogens would be opportunistic, not causal, sneaking across the blood-brain barrier and taking up residence only after Alzheimer’s has developed.

None of the earlier claims that infectious agents spur the development of Alzheimer’s “has held up after rigorous evaluation across multiple laboratories,” said Dr. Lennart Mucke, director of the Gladstone Institute of Neurological Disease. Moreover, he added, previous studies showed only an association, not causation.

But Dudley and his colleagues took a step toward showing causation, and therefore going beyond previous research, by finding that viruses had also slipped their genes into the DNA of cells in the Alzheimer’s brains. The viral genes seem to influence the expression, or activity, of genes associated with Alzheimer’s, including such famous ones as presenilin-1, BACE1, and several that direct the production of amyloid beta precursor proteins.

Steve's Take: New study showing causation between viruses and #Alzheimer's could be a major breakthrough and providing #hope for a cure
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The viral genes, Dudley said, seem to be activating proteins that in turn activate the Alzheimer’s genes, perhaps “acting as an environmental trigger to some of the genetic risk markers.”

Another hint of causation: “Viruses are overrepresented in the worst cases of Alzheimer’s, and seem to track the severity of disease,” said co-author Sam Gandy said.

Herpes viruses are extremely common. HHV-6 is found “in pretty much everybody over 2,” said Robert Moir of Massachusetts General Hospital, co-author of a paper on HHV6 and Alzheimer’s that will appear next month in Neuron. (Like Dudley’s, it took more than a year to be published, including time lost when the journal Cell initially accepted it for review and then rejected it.)

But clearly not everyone who carries herpes virus (which often stays dormant for years ) develops Alzheimer’s. That may be because the viruses don’t usually cross the blood-brain barrier (though there is some evidence they can get in from the nose via the olfactory nerve). But in some people, for unknown reasons, they might.

Bottom Line:

What this all might mean for Alzheimer’s treatment isn’t clear, STAT rightly observes. The new paper “raises a lot of questions that we should be looking at,” said Heather Snyder of the Alzheimer’s Association, “including [Alzheimer’s-causing] mechanisms involving the immune system.”

At minimum, said neuroscientist Miroslaw Mackiewicz of the National Institute on Aging, the study should make scientists consider “drug targets that are above and beyond” those involved in producing amyloid-beta.

There’s also a simple treatment idea, suggested by a little-noticed study published in April, 2018. Scientists in Taiwan followed 8,362 people who were diagnosed with herpes infections in 2000, and 25,086 people without the infections. The herpes-infected group was 2.6 times as likely to develop dementia. But in people treated with antiviral drugs, that risk was reduced by 90%.

Borrowing from Ms. Julie Yip-Williams, writer of a candid blog on colon cancer who died at 42, Alzheimer’s, like cancer, “crushes hope, leaving a wasteland of grief, depression, despair and a sense of unending futility,” she wrote in 2014. “Hope is a funny thing, though. It seems to have a life and will of its own.”

Of course, it is hope that keeps scientists and patients pressing forever forward toward a cure for Alzheimer’s, no matter how much time and frustration must be endured, aside from the staggering research costs. Perhaps this latest finding will turn out to be a positive step in that direction–unlike its multitude of forebears. I hope so.