Two herpes viruses appear to interact with genes connected to Alzheimer's disease—potentially playing a role in the disease's development and progression, according to study published Thursday in Neuron.
For the study, a team of researchers tested a long-held theory that certain infections might be linked to Alzheimer's. To examine the theory, the researchers used genomic sequencing technology to analyze more than 600 human brain samples of patients with and without Alzheimer's from brain banks.
The researchers examined the samples to identify genes present for patients with and without Alzheimer's—and then determined whether an association existed between the genes and the disease's development. Ultimately, the researchers measured the presence of viruses—which Sam Gandy, a senior author on the study, said they "did not expect"—and created a network to model how viruses might interact with human genes and have an effect on Alzheimer's, MedPage Today reports.
Joel Dudley, a senior author on the study and an associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York, said the researchers essentially "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. If the viruses are tweeting, who's tweeting back?"
According to Gandy, the researchers had started by "looking for genes that were dysregulated during the progression of Alzheimer's disease," but "what [they] found was that the most dysregulated sequences were not from the brain itself, but from the genomes of" human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7)—which are two common herpes viruses that typically infect people when they are infants and remain dormant for several years.
The researchers said they did not find evidence showing the two Herpes viruses cause Alzheimer's disease, but their findings suggest the two herpes viruses could be responsible for initiating an immune response that might lead to an increased accumulation of amyloid—the protein that forms into Alzheimer's plaques in the brain. In particular, when the researchers modeled how HHV-6A and HHV-7 interact with human genes, they found significant overlap between virus-host interactions and genes linked to Alzheimer's risk, MedPage Today reports.
What the findings might mean
Dudley said, "These viruses are probably significant players in driving the immune system in Alzheimer's. I think they're like gas on the flames of some pathology that may be immune-driven."
Gandy said, "We don't know yet whether they're integrated or whether they're separate, but certainly there's a fairly robust association of these genomes in the brains of patients with Alzheimer's."
John Morris—who directs the Knight Alzheimer's Disease Research Center at Washington University School of Medicine in St. Louis, but who was not involved in the research—said, "This definitely brings up the potential role of infection or infectious particles in the pathology of Alzheimer's," providing the most compelling evidence to date on the connection between Alzheimer's and infection or infectious particles. Morris said, "It's a very complex disease, and the answer's not going to be one thing. If viruses are a part of that, we definitely need to take a look at it."
Gandy said, "It's conceivable there are ways in which viruses interact that we haven't really taken very seriously before, in terms of provoking the pathology or the expression of disease. It could be that things are not as binary as we thought, that viruses act one way and genes another. It could be that viruses act through genes."
However, most Alzheimer's experts continue to question whether viruses are involved in the disease's development and progression or if viruses are product of the disease—or even, according to Lennart Mucke, director of the Gladstone Institute of Neurological Disease in San Francisco, simply "innocent bystanders," the Times reports.
Mucke called the study "impressive and very well designed," but said, "There have been many speculations and even outright claims that infections contribute to the development of Alzheimer's disease," and "none of them has held up after rigorous cause-effect evaluations."
Richard Hodes, director of the National Institute on Aging, said, "The data are very provocative, but fall short of showing a direct causal role and if viral infections are playing a part, they are not the sole actor." He continued, "The more we learn about the disease process and the more targets we can address the greater the probability we are going to slow or prevent the progression of Alzheimer's disease" (Belluck, New York Times, 6/21; Hamilton, "Shots," NPR, 6/21; George, MedPage Today, 6/21; Healy, Los Angeles Times, 6/21).
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