Over 30 years ago, UK-based molecular neurobiologist Professor Ruth Itzhaki and her colleagues discovered that herpes simplex virus type-1 could be present in the brains of older people.

Later, they found that people with both the APOE-e4 gene variant and HSV1 had significantly greater risk of Alzheimer’s disease. Further research showed that brain cells infected with HSV1 produced amyloid— and the virus’s DNA has since been found inside clumps of Amyloid proteins, which are markers of Alzheimer’s disease.

“We believe that the virus stays mainly dormant in the body for years – possibly decades. But later in life, as the immune system gets weaker, it can enter the brain and reactivate there. When it does, it will damage brain cells and trigger inflammation. Over time, repeated flare-ups could gradually cause the kind of damage that leads to Alzheimer’s in some people,” Professor Itzhaki explained in the Conversation last week.

“Large population studies by others found that severe infections, specifically with the cold sore virus, was a strong predictor of Alzheimer’s, and that specific antiviral treatment reduced the risk,” she continued.

What about other viruses?

Further research by Professor Itzhaki and her colleagues – as well as a new study led by a team at Standford University – has found that while people who had shingles had only a slight, non-statistically significant increased risk of developing dementia, those who had Zostavax were less likely to develop dementia.

“Consistently, studies by others showed that infections were indeed a risk and that some other vaccines were protective against Alzheimer’s,” Professor Itzhaki wrote.

“We then explored how risk factors for Alzheimer’s such as infections and head injuries could trigger the hidden virus in the brain.”

When her team introduced other infections or a simulated brain injury into a 3D model of the brain with a dormant herpes infection, HSV1 reactivated and caused damage similar to what occurs in the brains of people with Alzheimer’s disease. However, a treatment that reduced inflammation kept the virus inactive and prevented the damage.

“All of this suggests that the virus that causes cold sores could be an important contributor to Alzheimer’s, especially in people with certain genetic risk factors,” Professor Itzhaki added.

“It also opens the door to possible new ways of preventing the disease, such as vaccines or antiviral treatments that stop the virus from waking up and harming the brain.”

So what does all this mean in practice?

Associate Professor Michael Woodward, Head of Aged Care Research and the Memory Clinic at Austin Health in Melbourne, says the research should be interpreted with caution.

“The problem is that HSV1 has been implicated as a potential cause of dementia, particularly Alzheimer’s disease, several decades now. And whilst it is true that we can find viral fragments in the brain from HSV1, there are many other viruses that are found in all sorts of tissues throughout the body. That’s the nature of viruses.”

“That does not imply causation. And in fact, there’s been very little strong scientific evidence to prove that HSV1 is a cause or even a predisposing factor for dementia.”

Stronger evidence to support shingles vaccination

However, Associate Professor Woodward says the link between shingles vaccination and dementia prevention is “better evidenced,” but notes that “we do not know the mechanism.”

And while vaccinating against shingles may reduce the risk of dementia, it definitely won’t have any effect on HSV1, he adds.

“The vaccination against herpes varicella zoster virus seems to reduce dementia risk, but there’s no good evidence that the shingles virus in the brain causes dementia. It’s probable that vaccination has another effect that we haven’t fully teased out yet,” he says.