Alzheimer's disease affects millions of people around the world, but what ultimately causes the debilitating dementia remains unknown. One controversial theory, however, holds that the disease might be the result of a virus, or multiple viruses, infecting the brain.
Now, a new study offers more evidence to bolster this theory. In the study, published today (June 21) in the journal Neuron, researchers found that the brains of deceased people with Alzheimer's disease had higher levels of viruses than the brains of deceased people without Alzheimer's. Specifically, the Alzheimer's brains had up to twice as much of two common strains of herpes viruses than the non-Alzheimer's brains. [6 Big Mysteries of Alzheimer's Disease]
The theory that viruses or other pathogens could play a role in the development of Alzheimer's "is actually a pretty old idea," said lead study author Dr. Benjamin Readhead, an assistant research professor at Arizona State University and adjunct faculty member at the Icahn School of Medicine at Mount Sinai. "Even as early as the 1950s, people have been … positing the potential for some kind of pathogen to be contributing to Alzheimer's disease." Still, these ideas have received much backlash from scientists and medical experts throughout the years.
Readhead and his team didn't set out to look for possible viruses; rather, at first they were trying to find brain networks that existing drugs could be repurposed to target as potential treatments for the disease. "That actually kind of led us down this rabbit hole where we started suspecting that viruses could [explain] some of what we were seeing in these Alzheimer's disease networks," Readhead told Live Science.
In the study — one of the most detailed analyses of Alzheimer's brain tissue done to date — the team analyzed nearly 1,000 postmortem brains of people with and without Alzheimer's disease from multiple brain banks. They sifted through raw RNA and DNA sequences taken from these brain tissues and identified which of these genetic sequences were human and which were not. The non-human genetic sequences were compared to a database that contained genetic data for more 500 different viruses that researchers know can, or are thought to, affect humans.
The herpes virus
Though the idea of a virus or bacterium playing a role in Alzheimer's development has not been historically well-regarded, previous research has looked at the idea. In particular, past research has pointed to connections between Alzheimer's disease and the herpes simplex virus one, or HSV1 (the form of herpes virus that typically causes cold sores).
But in the new study, two different strains of the herpes virus stood out: herpes 6A and herpes 7.
And while it may sound startling to learn that there are strains of herpes in the brain, "the thing to say about these viruses is that they're very, very common," Readhead said. (Nearly everyone carries these herpes strains in their bodies because they are infected with them in infancy. However, the strains don't typically cause problems other than rashes in young children.) In fact, the researchers detected the presence of these viruses in about 40 to 50 percent of the brain tissues examined in the study. But the Alzheimer's brain samples had many more copies of these viruses than those without, he said.
Because viruses were found in both Alzheimer's brain tissue and non-Alzheimer's brain tissue, the researchers can't "simply say that infection with these viruses causes Alzheimer's disease," Readhead said. "There's obviously some other important mechanisms that change why some people would have a different response to the presence of a virus."
Still, the viruses may play a role: They could be part of the cause, or they could also just serve to accelerate the disease, Readhead said. Or maybe they don't play a role at all, and just happen to be along for the ride, he added.
To better elucidate the role, if any, of the viruses, the researchers looked to see if any of the viruses were affecting proteins and genes known to be implicated in Alzheimer's.
"There were actually quite a few different viruses that we saw [connected] in some interesting ways to different aspects of Alzheimer's," Readhead said. For example, the herpes 6A virus was found to interact with a large number of genes linked to Alzheimer's disease risk, as well as genes related to amyloid plaques, which are protein clumps that form in the brains of people with the disease.
Still, more research is needed. "One of the real outstanding questions to this is trying to determine the extent [to which] what we're seeing could be a causal contributor to the disease," Readhead said.
But which herpes virus is it?
Hugo Lövheim, a senior lecturer in the Department of Community Medicine and Rehabilitation at Umeå University in Sweden who was not part of the study, praised the new research.
"The authors have performed a really impressive in-depth analysis of postmortem Alzheimer’s disease brain tissue samples using modern bioinformatics techniques," Lövheim told Live Science. "This is in line with the now rapidly increasing evidence of viral infections as key drivers in the development of Alzheimer’s disease pathology." [9 Surprising Risk Factors for Dementia]
However, Lövheim noted that he still believes HSV1 "is a more likely cause of the disease" at its onset. The new study, along with some earlier research, he said, indicates that the herpes 6A virus may play a role at least in late Alzheimer’s disease. Therefore, future Alzheimer's drug research could aim to target both strains of the virus, he said.
Ruth Itzhaki, a professor emeritus of neuroscience and experimental psychology at the University of Manchester in England was also not a part of the new study, but was the first researcher to point to the possible role of HSV1 in Alzheimer's, back in 1991.
Itzhaki told Live Science in an email that she still thinks HSV1 has a stronger link to Alzheimer's, but that the viruses could be working together.
"It’s good that the viral concept is now being taken seriously, because during almost all of 28 years, I and subsequently others have suffered venomous hostility, derision or neglect from influential people in the field," she said.
Originally published on Live Science.
