If you've ever had a common cold sore you might be at greater risk for eventually developing Alzheimer's disease (AD). Terrifying though this may seem, the link could wind up providing better treatment options for Alzheimer's patients. This information comes thanks to a review of decades worth of research, which was published in the Oct. 19, 2018, issue of the journal Frontiers in Ageing Neuroscience. Since 67 percent of the global population under age 50 contracts HSV1, which causes cold sores, at some point in their lives, a vaccine would be a win/win.
"My lab started work on this topic in 1989 and it was the only one in the world for about 15 years, as there was so much opposition to the concept [of a link between the herpes virus and contracting Alzheimer's]," says Ruth Itzhaki, professor emeritus of molecular neurobiology at the University of Manchester in England, who authored the review. "Funding was therefore extremely hard to get and publishing the work was extremely difficult. Eventually, more people did enter the field and now there are well over 150 supportive publications."
Itzhaki explains via email that the connection was first made years ago thanks to research that discovered herpes simplex encephalitis — an extremely rare brain disease triggered by HSV1 — affects the same regions of the brain as AD. Indeed, the link makes sense despite the drastically different presentations of both diseases. (AD is hallmarked by memory, decision-making and other cognitive problems, whereas HSV1 is a virus that causes painful cold sores and fever blisters.) Since so many people experience dementia, Itzhaki notes that any microbe implicated in the disease would have to be a very common one, so HSV1 fit the bill. The very nature of HSV1's typically dormant state also makes it a credible culprit.
"Presumably, the virus must remain lifelong latent (i.e., dormant) in the body to be able to cause damage perhaps years after infection," she says. "It infects most humans in infancy and thereafter remains lifelong in the body in latent (i.e., dormant) form within the peripheral nervous system (PNS — the part other than the brain and the spinal cord)."
Ithaki's previous work had shown that cold sores occurred more often in people who carried APOE-E4, a gene variant that also carried an increased risk of Alzheimer's. Her theory is that in APOE-E4 carriers, reactivation from stress, immunosuppression or brain inflammation is more frequent or more harmful in HSV1-infected brain cells and the resulting damage contributes to the development of Alzheimer's, particularly as people age and their immune systems decline.
"Presumably, in APOE-E4 carriers, Alzheimer's disease develops in the brain because of greater HSV1-induced formation of toxic products, or lesser repair of damage," Ithaki writes in The Conversation.
She notes that previous studies, including her own, only showed a link between the herpes virus and Alzheimer's, but not that the virus caused AD. However, three studies were published in 2017 and 2018 using data from Taiwan's National Health Insurance Research Database, which enrolls 99.9 percent of that country's population, to research this topic.
"The striking results include evidence that the risk of senile dementia is much greater in those who are infected with HSV, and that anti-herpes antiviral treatment causes a dramatic decrease in number of those subjects severely affected by HSV1 who later develop dementia," she notes in a press release. However, these Taiwanese studies only applied to people with severe HSV1 infections, which are rare.
The next steps, she says, are setting up a clinical trial in the U.K. using antiherpes antiviral agents to treat Alzheimer's patients and finding out whether any other microbes are involved in the disease.