A herpes virus can hang out, dormant, in the gut. But new research suggests it might be sneaking up the vagus nerve and into the brain, where it could spark the onset of Alzheimer's.
Can a seemingly harmless virus in the gut wreak havoc on the brain decades after the initial infection? And could catching and treating an infection early mean Alzheimer’s prevention? These are the questions spurred by research recently published in the journal Alzheimer’s and Dementia, which point to a potential link between chronic, viral gut infections from the Herpes family and Alzheimer’s disease.
It’s among the latest evidence in a growing mound of research that shows viruses and bacteria might play a critical role in driving neurodegenerative diseases. But before digging into the study, it’s important to first take a step back and ask a more fundamental question:
Can viruses cause Alzheimer’s?
Answering that question is complicated, in part because scientists still aren’t sure what Alzheimer’s disease is … or whether Alzheimer’s is too broad a term. Scientists have long suspected that what we currently think of as Alzheimer’s might actually be comprised of multiple subtypes, stemming from a range of contributing factors that range from genetic disposition and lifestyle choices to immune system problems, and, yes, viral infections. The latter, also known as Alzheimer’s viral theory, suggests that viruses play a role in triggering an immune response and/or directly infecting brain cells in a way that leads to a build up of Alzheimer’s key biomarkers: beta-amyloid plaques and tau tangles. To date, a lot of the research into Alzheimer’s viral theory has focused on herpes simplex virus. The recent study homed in on a different, though widely common, member of the herpesvirus family: cytomegalovirus (HCMV).
Up to 90 percent of people are carriers of a dormant HCMV infection by the time they turn 80. But if HCMV infects the gut, how might it be playing a role in a brain disease?
“That gut infection seems to be … a risk factor for eventual passage into the brain,” explained associate research professor at Arizona State University Ben Readhead, who co-led the study. Readhead and colleagues tracked how HCMV could potentially travel up the vagus nerve, the pathway that connects the brain to the large intestine.
What happens in vagus therefore may not stay in vagus, as the brain’s immune cells kick into action. In fact, nearly half of the people with Alzheimer’s in the study had brain cells known as microglia equipped with a protein called CD83. When those cells recognize something harmful in the brain, they use CD83 to prepare for battle, stimulating an immune response.
Tipped off by that immune system activity, the researchers looked for antibodies that might explain their findings. “We began to wonder about whether or not there might be some microbial perturbation that could be explaining this,” Readhead said, after reviewing the autopsied brains of people who died from Alzheimer’s.
Using biopsies of the participants’ colon, vagus nerve, and samples of cerebrospinal fluid, the researchers did discover a specific antibody (called IgG4) that recognized HCMV.
Next, researchers grew mini-brains in a dish and infected them with HCMV. They found that the HCMV infection hastened the production of Alzheimer’s biomarker proteins tau and amyloid.
“I think it’s possible that this particular virus in a subset of people kind of tips them into a disease state,” Readhead said.
To figure that out, scientists would need to run clinical trials that spot people in the early stages of Alzheimer’s disease with an unresolved infection, and then test to see whether treating the infection with antiviral medications might slow the progression of the disease.
Readhead and his team believe that would be the best next step to showing how detecting an infection of HCMV early on, and treating it, could help safeguard cognitive health.
Lavinia Alberi, lead neuroscientist at the Swiss Integrative Center for Human Health, who was not involved in the study, agrees that — if future research supports that the virus reactivates before cognitive symptoms occur — treating the infection could help prevent or slow Alzheimer’s. Funding for new research in “infection-focused approaches,” she explained, “is crucial for advancing Alzheimer’s Disease treatment paradigms.”
What’s next for HCMV and Alzheimer’s research?
Will McEwan, a professor at the UK Dementia Research Institute at the University of Cambridge, told the Science Media Center that the team’s findings are “very interesting,” but they leave many questions unanswered.
“The study does not address how common this infection is in people without Alzheimer’s, and therefore cannot by itself suggest that HCMV infection, or the associated immune response, is a driver of disease,“ he explained.
Readhead also acknowledged the limitations of the study and the need for more research. The study examined only a small amount of post-mortem tissue, which included brain and gut tissue, as well as vagus nerve samples. Researchers say they need to look at more people from different ethnic backgrounds and countries to independently confirm these findings. But, if the findings hold true, they could fuel investment into a new class of Alzheimer’s treatments that include antimicrobial and antiviral agents.
One such trial is already underway. It focuses on antiviral drugs targeting Herpes in people with mild Alzheimer’s disease and their impact on the levels of plaques in the brain. The study concluded in December 2024, but researchers have yet to share the results.
I am 83 yrs. old. I have APOE 2 & 3 . I also have PHN after having chicken pox as a child. I am worried about dementia, My PHN affects the right side of my head as well as my right eye. Is this virus connected to dementia? PLZ reply to thebun@cfl.rr.com . THank You. Mary M.
Hi Mary, thanks for getting in touch. Sorry to hear that you had complications after chicken pox. Scientists have studied large populations of people to look for links between chicken pox and dementia but so far, there isn’t anything very conclusive. Some studies suggest that people who receive a chicken pox vaccine might be less likely to develop dementia. Some researchers think that viruses can spark processes in the brain that might lead to dementia, but these are still ideas that haven’t been confirmed. Viruses like chicken pox might be one small contributing factor toward your dementia risk — but other factors like age and sex play a much stronger role. If you have concerns about your risk, we recommend you speak with your doctor.
I always wonder about the extent to which ALL viruses potentially play a role in illness. ( Epstein Barr, Lyme, Covid and others.. )
Is there any pathology data breaking down percentages of those deceased with Alzheimers and the virus(es) had?
Thank you!
Hi Paula, that’s a very interesting question. Even though most of us might harbor these viruses, they remain dormant and asymptomatic. That means when we look at samples of postmortem brains from people with dementia, we might see a lot of people who may have had an infection but we don’t know whether this is higher or lower than in the general population. It is also hard to tell whether the infection was active at the time, whether it was sparked by dementia, or whether the brain’s immune system spent so much energy focusing on fighting off dementia that it neglected the viruses. There’s still many ongoing studies that may one day tell us which viruses might play an important role.