January 7, 2025

expert reaction to study of human brain tissue reporting that injury reactivates latent HSV-1 virus and induces changes associated with Alzheimer’s disease

A study published in Science Signalling looks at brain tissue injury in a dish, and the reactivation of latent HSV-1 virus that may induces changes associated with Alzheimer’s.

Dr Julia Dudley, Head of Research Strategy at Alzheimer’s Research UK, said:

“These two studies offer new insights into how a common herpes virus could contribute to the early stages of Alzheimer’s disease in some people, by affecting the brain’s immune system.

“One study found that changes to a protein in the brain called tau, which is linked to Alzheimer’s, may happen as part of the immune system’s response to this virus. The other study shows how repeated mild head injuries could reactivate the virus, triggering brain changes seen in diseases like Alzheimer’s.

“It is too early to say if there is a strong link between the herpes virus, traumatic brain injury and Alzheimer’s. The researchers used cell models for their experiments, and further investigation is needed to see whether these results apply to people.

“That said, studies like these highlight new treatment avenues, such as using medicines that target these viruses or reduce harmful inflammation in the brain. Understanding the first changes in Alzheimer’s disease could help provide the crucial first steps towards a cure.”

Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and President of the British Neuroscience Association said:

“This paper by Cairns and colleagues explored the potential relationship between latent herpes simplex virus type 1 infection, injury, and Alzheimer’s disease pathology. The scientists used human stem cells reprogrammed to mimic brain cell types grown in a sponge which were infected with the virus then either directly poked with a cylinder or hit while in a closed container to mimic brain injury.  While this is an interesting and important topic, the study has several important limitations to consider. The increase in Alzheimer’s like brain changes in these latent virus-containing cells subjected to injury do not resemble the pathology that is found in the brain of people with Alzheimer’s disease.  These experiments were also in cells grown in artificial conditions without important Alzheimer’s-related factors such as age and blood vessel changes.  Finally, these experiments were repeated in a small number of experimental replicates (3 times per experiment), so these results will need to be confirmed in more relevant biological systems with larger studies to be sure there is a biological link between latent herpes simplex virus type 1, brain injury, and Alzheimer’s pathology.”

Prof Robert Howard, Professor of Old Age Psychiatry, UCL Division of Psychiatry, UCL, said:

“The study is interesting and raises a potential mechanism for the observed association between infection with the cold sore virus, brain injuries and Alzheimer’s disease. However, as so often in science, it is very important to bear in mind that association does not mean causation. Much more research will be needed before this can be seriously considered a plausible mechanism for the development of dementia. Avoidance of brain injuries, such as those encountered in some contact sports, is already known to be an important way to prevent dementia and I’m unconvinced that this reflects anything more complicated than mechanical damage causing death of brain cells.” 

Prof Jennifer Pocock, Professor of Cellular Neuroscience, UCL Queen Square Institute of Neurology, said:

“This is an interesting paper, but the authors don’t seem to have considered the role of microglia. Microglia are cells in the brain which are known to be activated by mild traumatic brain injury (TBI) and repetitive TBI. This paper seems to suggest that only astrocytes contribute to the reported neuroinflammation in brain tissue. Also, the inclusion of APOE3/4 is not clearly defined. Because of this, the findings are likely to represent an overinterpretation for the “real world” as the inclusion of microglia may negate or accentuate them, depending on the severity of the TBI.” 

‘Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model’ by Dana Cairns et al. was published in Science Signaling at 19:00 UK time on Tuesday 7^th January. 

DOI: www.science.org/doi/10.1126/scisignal.ado6430

Declared interests

Prof Tara Spires-Jones: I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.

Prof Robert Howard: No COIs

Prof Jennifer Pocock: I receive research funding from AstraZeneca and Daiichi Sankyo.

For all other experts, no reply to our request for DOIs was received.