Exploring the causal link between herpes and Alzheimer’s 

The scientific community remains divided over the origins of Alzheimer’s disease.

Arguably the most prevailing theory amongst researchers is that the disease is caused by a build-up of amyloid leading to damage to nerve cells in the brain. Known as the amyloid cascade hypothesis, it has formed a central plank of Alzheimer’s research for the best part of three decades.

However, with a breakthrough as to a cure yet to arrive, some believe pumping more funding into the amyloid hypothesis threatens to create a research cul-de-sac of counter-productivity. 

Dr Ruth Itzhaki, professor emeritus of molecular neurobiology at University of Manchester, is one such researcher who believes there has been an over-focus on amyloids at the expense of other areas of research into the causes of Alzheimer’s.

“In one ten-year period there has been something like 400 trials based around the amyloid hypothesis,” she says. “They’ve cost a lot of money and none of them have worked. I’d also say there has been overemphasis on tau, another abnormal feature of Alzheimer’s on the brain, which hasn’t gotten us very far. It’s very puzzling.”

Itzhaki has instead chosen to focus her own research on the correlation between the herpes virus (Herpes Simplex Virus 1) and the risk of people developing Alzheimer’s later in life.

On the back of 25 years of research, Itzhaki published a paper last year in Frontiers in Ageing Neuroscience arguing that the causal link between the virus and senile dementia is too strong to ignore, as underscored by new epidemiological data.

Herpes – best known for giving cold sores – predominantly infects people during infancy and remains dormant in the peripheral system, manifesting itself only occasionally (often in the event of stress). According to Itzhaki’s research, many elderly people were found to have a presence of HSV1 in the brain – conferring a strong risk of Alzheimer’s disease when present in the brain of individuals with the apolipoprotein E4 gene (ApoE4).

Itzhaki believes herpes can therefore become active in the brain, resulting in the corrosion of brain cells. The chance of developing Alzheimer’s is “12 times more likely” for ApoE4 carriers who have HSV1 in the brain than those without either factor.

She also believes the virus could account for up to 50% of Alzheimer's disease cases. If this is the case, the huge question raised is whether simple anti-viral drugs could be used to treat a disease suffered by more than 30 million people worldwide, and commonly considered to be the scourge of our times.

“These findings do indicate anti-viral agents might provide an answer as to a cure for Alzheimer’s,” affirms Itzhaki. “We already have some drugs which are fairly specific in the treatment of the herpes virus. So, we do feel there is huge potential here.”

Nonetheless, Itzhaki has been in the research game for far too long to get carried away. While the results of her research may have been recently picked up by the mainstream media, (“it’s quite flattering, I suppose”) as the breakthrough we’ve all been waiting for, she is realistic enough to issue several caveats.

First off, she says she has felt a distinct lack of support for her work from some of her peers in the Alzheimer’s research field, to whom she refers as the “amyloid die-hards”.

“There has been so much hostility and opposition – not to mention a lack of financial support,” explains Itzhaki. “Most of these people have spent a long time working on the amyloid hypothesis, and I don’t think they like the idea of their research being overturned.”

Itzhaki has concerns that such opposition may create a stonewall in pushing ahead with a clinical trial, for which she is putting together an application. “I’m just hoping we don’t have any anti-microbial die-hards refereeing it,” she says.

Then there’s the rub of accumulating enough population health data to prove her theory. Few countries, including the UK, collect such data needed to demonstrate if antiviral drugs reduce the risks of dementia.

There are exceptions, though. Itzhaki points to Taiwan where 99.9% of the population are enrolled in a national health insurance research database, which has been widely mined for information on microbial infections and diseases. Three recent studies, based around this data, showed strong evidence that the risk of senile dementia is greater in those with HSV, and that anti-viral treatment was responsible for a drop in the number of subjects affected by HSV1 who developed Alzheimer’s later in life.

While she believes the results to be “encouraging”, Itzhaki admits they should be qualified by the fact that the Taiwanese studies only relate to severe HSV1 infections, which are comparatively rare. In an ideal world, researchers would be able to train their focus on dementia rates amongst those with milder cases of the virus.

“The link between viruses – such as herpes – and dementia is interesting, but we have a way to go in our understanding of how these infections affect the brain,” says Professor Bart de Strooper, director of the UK Dementia Research Institute, in reference to Itzhaki’s research.

“These studies suggest that herpes is more common in the brains of people with Alzheimer’s than in those with healthy brain. However, whilst there may be a correlation between having the two conditions, it’s essential that we determine if there is a true underlying biological link. Only then we will be able to say if there is a true connection.”

According to Maria Carrillo, chief science officer at the US-based Alzheimer’s Association, the link between herpes viruses and Alzheimer’s is “not new”, although the main talking point that persists is whether such viruses are causal or symptomatic of the condition.

“Possible roles for microbes and viruses in Alzheimer's disease have been suggested and studied for decades,” she says. “The primary question is whether they play an active, causative role in the disease, or instead take advantage of the damage caused by Alzheimer’s to enter the brain as opportunistic passenger. More research is needed to discover exactly what roles, if any, they play.”

Amidst the flurry of wider interest in her research, Itzhaki has been approached by members of the public with relatives with Alzheimer’s. She admits at being at a loss to what to say and what to promise them, “because I’m not a doctor, and you can’t just have people dosing their relatives up with anti-virals, can you?”

“I can’t honestly put my hand on my heart and say that we’ve come up with the cure for Alzheimer’s,” she continues. “But there’s a decent argument to say that it could work. It’d be wonderful if it did.”