A recent study found a possible connection between the herpes simplex virus-1 (HSV-1) and Alzheimer’s. It also discovered that the tau protein in the brain, the hallmark of this neurodegenerative disease, may initially defend against viral infections.
According to estimates, the worldwide dementia population will reach 153 million by 2050 [1]. Therefore, researchers are focusing on identifying health factors and disorders that may raise a person’s risk of developing dementia, particularly Alzheimer’s.
Identifying health factors that increase a person’s risk of Alzheimer’s disease is critical since it enables early intervention, targeted preventative initiatives, and personalized therapeutic strategies.
A new study published in the journal Cell Reports has implied a link between Herpes simplex virus-1 (HSV-1) and Alzheimer’s [2].
The brain’s tau protein, which has long been thought to be a sign of Alzheimer’s, may actually guard against viral infections before causing brain damage later in life, according to the study.
How are HSV-1, tau protein, and Alzheimer’s linked?
For this study, the research team looked into potential connections between HSV-1 and Alzheimer’s disease using several modeling techniques.
The study’s senior author, Shemesh, PhD, an assistant professor in The University of Pittsburgh’s Department of Ophthalmology, explained that clumps of the proteins tau and beta-amyloid outside brain cells are typically used to diagnose Alzheimer’s.
He added that tau is found to be modified and pathogenic in the disease. According to recent studies, infections may contribute to Alzheimer’s disease, and HSV-1 is a prime suspect [3].
In the latest study, the researchers identified HSV-1-related proteins in autopsy human brain samples. They discovered that viral proteins are present in the same regions as tau but not with beta-amyloid and increase as Alzheimer’s progresses. In tests employing tiny human brain models (organoids), they discovered that tau levels rise in response to HSV-1 infection.
According to Shemesh, it is interesting that the modified tau seems to decrease herpes protein levels and the number of neurons that die following infection as if the neurons were completely uninfected.
This prompted the researchers to investigate the cGAS-STING pathway [4], a particular immune response mechanism in the brain. They discovered that molecules from this pathway exist where HSV-1 and modified tau are detected in Alzheimer’s.
The researchers also demonstrated that activating this immunological pathway increases tau modification while inhibiting it stops tau modification. According to Shemesh, these findings imply that tau might be a component of the brain’s immune response in Alzheimer’s and that therapeutic measures could focus on assisting rather than obstructing it.
Potential for new Alzheimer’s treatment
Shemesh claims that these discoveries might eventually result in novel approaches to Alzheimer’s treatment.
According to him, the finding that tau phosphorylation may function as a protective mechanism against HSV-1 infection implies that boosting this immune response could help reduce the effects of viral infections in the brain, which are increasingly being connected to Alzheimer’s pathogenesis. Mimicking tau phosphorylation’s positive effects without causing its detrimental aggregation, which is linked to the advancement of Alzheimer’s, may be a promising approach.
He went on to say that this method could assist in boosting the brain’s innate immune response while preventing the production of neurofibrillary tangles, which aggravate the condition. By comprehending the precise processes by which tau offers this defense, scientists can develop treatment approaches that maximize its beneficial functions while reducing its deleterious impacts on neuronal health.
What’s next?
Shemesh asserts that by recognizing the risk factors, scientists may create strategies to reduce them, which may delay or stop Alzheimer’s from developing. Furthermore, this data advances the understanding of the disease’s mechanisms, which may result in the identification of new therapeutic targets and enhanced diagnostic capabilities.
The research team plans to delve deeper into the mechanisms behind tau’s protective role, study other pathogens that may interact with tau or beta-amyloid in Alzheimer’s, and test possible therapeutics that may leverage or imitate tau’s protective properties.
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References
- Nichols, E., Steinmetz, J.D., Vollset, S.E., Fukutaki, K., Chalek, J., Abd-Allah, F., Abdoli, A., Abualhasan, A., Abu-Gharbieh, E., Akram, T.T. and Al Hamad, H., 2022. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. The Lancet Public Health, 7(2), pp.e105-e125.
- Hyde, V.R., Zhou, C., Fernandez, J.R., Chatterjee, K., Ramakrishna, P., Lin, A., Fisher, G.W., Çeliker, O.T., Caldwell, J., Bender, O. and Sauer, P.J., 2025. Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease. Cell Reports, 44(1).
- Feng, S., Liu, Y., Zhou, Y., Shu, Z., Cheng, Z., Brenner, C. and Feng, P., 2023. Mechanistic insights into the role of herpes simplex virus 1 in Alzheimer’s disease. Frontiers in Aging Neuroscience, 15, p.1245904.
- Zhou, J., Zhuang, Z., Li, J. and Feng, Z., 2023. Significance of the cGAS-STING pathway in health and disease. International Journal of Molecular Sciences, 24(17), p.13316.
- Pelc, C. Is Alzheimer’s linked to the cold-sore-causing herpes virus? Medical News Daily. https://www.medicalnewstoday.com/articles/is-alzheimers-linked-to-cold-sore-herpes-virus. Published Online: 8th January 2025. Accessed: 6th February, 2025.
- Link Between Cold Sore Herpes Virus and Alzheimer’s Discovered. Neuroscience News. https://neurosciencenews.com/hsv-1-herpesvirus-alzheimers-28297/. Published Online: 2nd January 2025. Accessed: 6th February, 2025.
