June 21, 2018

expert reaction to study looking at herpes virus and Alzheimer’s disease

Scientists publishing in Neuron examine the relationship between human herpesviruses and Alzheimer’s.

Prof Ruth Itzhaki, Professor Emeritus of Molecular Neurobiology at the University of Manchester, and Honorary Senior Research Fellow at the University of Oxford, said:

“This study builds on previous studies which have found associations between herpes viruses and Alzheimer’s disease, some of which I carried out at the University of Manchester over the last number of years.  This new study actually implicates different herpes viruses from those that had been looked at previously, though a 2002 study from my lab suggested that human herpesvirus type 6 (HHV6) might be involved as well as herpes simplex virus type 1 (HSV1).  Most elderly people have these viruses in their brains anyway, and not everyone develops Alzheimer’s disease, so the public should not be alarmed.

“This paper is clear that it alone cannot show that herpes viruses are a causal factor in Alzheimer’s disease development.  However, recent work from Taiwan looking at population-level epidemiology found a causal relationship in that that those infected with HSV1 have a high risk of developing Alzheimer’s disease, and that antiherpes antiviral treatment is strongly protective.  Thus, along with other previous work including my own, a picture is building up showing strong links between herpes viruses and the likelihood of developing Alzheimer’s disease.  A commentary which explains and interprets the findings of the Taiwan papers, by me and Richard Lathe, is currently in proof for the Journal of Alzheimer’s Disease.

“From the research in this field as a whole, it looks like a combination of HSV1 and a known genetic susceptibility to Alzheimer’s may be more likely to develop Alzheimer’s, and that some other herpes-type viruses may also play a part.

“We now need more research to establish whether these viruses are causally linked to Alzheimer’s, and whether using that information we might be able to develop treatments.”

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead, and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study led by Dr Joel Dudley at Mount Sinai hospital in New York found increased levels of human herpesvirus in the brains of people with Alzheimer’s disease compared to healthy people.  Their analyses were robust and indicated that these viruses could be contributing to the harmful brain changes that cause Alzheimer’s; however, it is also possible that people with Alzheimer’s are more susceptible to brain infections since the disease damages the barrier between the blood and the brain that usually protects the brain from infection.

“Thus while these data are very interesting and important for future research, they do not definitively support the idea that people with herpes are more likely to develop Alzheimer’s.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“The relationship between viruses and Alzheimer’s disease has been an area of interest for researchers for a while, but it is still unclear if higher levels of viruses cause dementia or are caused by it.

“In this study, researchers used sophisticated analysis to find that people with Alzheimer’s disease had higher levels of certain herpes viruses and the results also suggested that these viruses might affect genes in the brain that are linked to Alzheimer’s.

“However, similar to other studies in this area, while this is robust research, it could not prove that the viruses actually were responsible for the disease.  It therefore doesn’t change what we already know about the causes of dementia, doesn’t mean that having cold sores put you at increased risk of getting it and people shouldn’t be unduly worried.

“Alzheimer’s is a devastating disease and with no way to prevent, cure or even slow it down, it’s vital we pursue every avenue to stop it in its tracks – that’s why we’re continuing to increase our funding for research.  In the meantime, we know that people can reduce their chances of getting dementia by eating well, exercising regularly and avoiding smoking or heavy drinking.”

Prof Clive Ballard, Professor of Age-Related Diseases, University of Exeter Medical School, said:

“There is a 15 year history of association studies suggesting a possible link between certain viruses, such as herpes, and increased risk of Alzheimer’s disease.  This new study is however a vital step forward as it highlights specific disease related mechanisms.  This now gives the potential to investigate the impact of viruses more directly in experimental studies, so that we can really understand whether there may be important implications for treatment or prevention.”

Dr David Reynolds, Chief Scientific Officer of Alzheimer’s Research UK, said:

“These findings point to an association between two forms of the herpes virus and Alzheimer’s, but they don’t tell us that these viruses cause the disease.

“Previous studies have suggested that viruses might be linked with Alzheimer’s, but this detailed analysis of human brain tissue takes this research further, indicating a relationship between the viruses and the activity of genes involved in Alzheimer’s, as well as brain changes, molecular signals, and symptoms associated with the disease.  This was a well-conducted study and the authors’ findings were supported by evidence drawn from three independent sources of donated brain tissue.

“The viruses highlighted in this study are not the same as those that cause cold sores, but much more common forms of herpes that are among the many viruses that nearly everyone carries, and which don’t typically cause any problems.  While the findings indicate a link between the activity of these viruses and Alzheimer’s, they don’t tell us whether they contribute to the development of the disease, help the brain to cope with the disease, or just occur alongside Alzheimer’s-processes without having an impact on the health of the brain.

“In an experiment involving mice, the researchers reproduced an effect of one of these viruses – reduced activity of a gene called Mir155 – finding that it led to higher levels of the hallmark Alzheimer’s protein, amyloid.  The authors suggest their findings in mice support the idea of viral activity contributing to the development of Alzheimer’s, but their analysis of human brain tissue doesn’t give conclusive evidence about cause and effect.

“As almost everyone carries these viruses, the findings don’t provide any insight into an individual’s risk of Alzheimer’s, but they do highlight a need for future studies to explore the nature of the link.  This study in no way suggests that Alzheimer’s disease is contagious or can be passed from person to person like a virus.”

* ‘Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus’ by Ben Readhead et al. published in Neuron on Thursday 21 June 2018. 

Declared interests

Prof Ruth Itzhaki: “No competing interests.”

Prof Tara Spires-Jones: “I do not have any conflicts of interest with this work.”

Dr David Reynolds: “No conflicts.”

None others received.