A-beta plaque buildup could be the brain’s way of protecting itself from the virus
Joel Dudley and his colleagues were searching through datasets for Alzheimer’s disease vulnerabilities to exploit in creating a treatment when they stumbled across a surprising correlation: Many of the brains they looked at had signs of herpesvirus infection. But those from people with Alzheimer’s disease had much higher levels of viral DNA than those from healthy people.
In particular, the researchers found high levels of HHV-6 and HHV-7, two strains of herpesvirus associated with a common childhood illness called roseola, the team reports online June 21 in Neuron.
“We had no intention of looking at viruses,” says Dudley, a biomedical informatics researcher at the Icahn School of Medicine at Mount Sinai in New York City, who gives a talk jokingly titled, “I went looking for drugs and all I found were these stupid viruses.”
It is unclear whether the herpesviruses contribute to the development of Alzheimer’s, or if Alzheimer’s patients are just more susceptible to these viruses, which can remain latent in the body long after exposure. Genetic factors also influence a person’s risk of developing Alzheimer’s. The researchers did find that the viruses interacted with genes linked with Alzheimer’s disease, though the implications are still murky.
Dudley has now found himself in the middle of a debate between researchers who believe there is a link between infectious pathogens and the degenerative brain disease, and those who do not. One reason for the controversy, says James Leverenz, a neurologist at the Cleveland Clinic, is that herpesviruses “are so ubiquitous, and so many people carry them.” The idea that such a common virus could contribute to a devastating disease seemed unlikely to many researchers for decades.
Traditional research into Alzheimer’s — a disease that affects more than 5 million Americans — has focused on two primary traits of the disease: amyloid-beta plaques that collect between nerve cells in the brain, and tau tangles, twisted protein fibers that block communication between those nerve cells, or neurons (SN: 12/24/16, p. 27). But recent research suggests that A-beta, instead of being junk that clogs up spaces between brain cells, may actually function as a type of anti-microbial peptide, chains of amino acids that can trap pathogens.
A second new study now in press at Neuron suggests that A-beta peptides in Alzheimer’s patients could become over-activated by infections such as herpes, and form plaques in an effort to protect the brain. The paper’s hypothesis — referred to as “the antimicrobial protection hypothesis of Alzheimer’s disease” — is that herpes microbes trigger the A-beta buildup, which in turn triggers Alzheimer’s disease.
Rudolph Tanzi, a neurologist at Massachusetts General Hospital in Boston, and his colleagues found that A-beta plaque deposits form more quickly in mice injected with HSV-1, another common herpesvirus. These mice also experience less herpes-caused brain inflammation, suggesting that A-beta plays a role in the innate immune system. Though herpesvirus is most commonly linked to Alzheimer’s, other pathogens including bacteria and fungi could theoretically also trigger A-beta plaques, Tanzi says.
With mounting evidence of a potential link, traditional Alzheimer’s researchers might be more receptive to these findings than in the past, says Leverenz, who was not involved in either study. “Between the immune system [research] and the recognition that Alzheimer’s is very complex,” he says, “there’s probably a little more openness to examine this idea.”
Both papers stress that more work needs to be done to understand the connection between herpesvirus and Alzheimer’s. And it is unclear how a person’s genetics come into play with this new idea, says neuroscientist Keith Fargo at the Alzheimer’s Association in Chicago, who was not involved in either study (SN: 3/17/18, p. 8). “There are a lot of genetic factors that play a role” in Alzheimer’s disease, he says.
What we do know is that Alzheimer’s disease is not contagious, Dudley says. You cannot “catch” Alzheimer’s from someone experiencing dementia symptoms. Even if herpesviruses play a role, many other factors definitely contribute to developing this disease.
B. Readhead et al. Multiscape analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron. Published online June 21, 2018. doi: 10.1016/j.neuron.2018.05.023.
W. Eimer et al. Alzheimer’s disease-associated B-amyloid is rapidly seeded by herpesvirudae to protect against brain infection. Neuron, in press, 2018.
K. Bourgade et al. B-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1. Biogerontology. Vol 16, February 2015, p. 85. doi: 10.1007/s10522-014-9538-8.
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