One of the most common diseases in the world is herpes, as 50 to 80% of Americans have this illness. The herpes simplex virus, which causes cold sores, is normally transmitted through person-to-person contact. This illness leaves the patient with blisters clustered around the mouth. Gradually, the blisters pop and leave sores that take around one week to heal.
However, that is just the short-term effect of herpes. This virus hides in certain neurons in the mouth, occasionally reactivating to cause another bout of cold sores [1]. This permanent infection is known as latency, a trait that herpes shares with other viruses such as cytomegalovirus.
Familiar Alzheimer’s proteins
Researchers have noted a link between latent herpes infection and an increased incidence of cognitive decline. This decline is exacerbated by multiple activations, and this is especially true for carriers of the APOE4 allele, a genetic variation implicated in Alzheimer’s risk [2].
Immune responses to herpes infection are very similar to the hallmarks of Alzheimer’s [3]. Specifically, after infection with HSV-1, amyloid beta and tau tangles, two major hallmarks of Alzheimer’s, increase in concentration [4].
While these two proteins are influenced by herpes infection, they are primarily known for their impact on brain aging and neurodegeneration. With age, the misfolded form of amyloid beta protein, which controls neuronal growth and homeostasis, aggregates and forms plaques [5]. On the other hand, tau tangles are formed by a misfolded version of the protein tau, which normally influences neurons’ internal skeletons [6]. Both of these can disrupt cell-cell synaptic communication, contributing to the development of dementia.
An immune link
The link between herpes and dementia could also be related to the immune response that the body uses in an attempt to rid itself of this viral infection. Inflammation has previously been implicated as a driving factor behind age-related decline [7], specifically cellular senescence [8] and free radical production [9].
Fortunately, solutions to the immune components of age-related diseases are being investigated. Researchers are studying centenarians to figure out how they reduce inflammation-driven age-related damage (inflammaging) and incidences of age-related diseases [10]. With a greater understanding of how inflammation affects aging and better theories on the mechanisms behind this influence, researchers can develop new therapies to reduce the impact of these viral infections on dementia risk.
Overall, this is an actively progressing area of research, and there is still much work to be done to better understand the role that herpes simplex virus plays in dementia. However, there have been promising strides in better understanding and tackling the immune system’s role in aging and theories that link herpes to dementia-related processes.
Literature
[1] Nicoll, M. P., Proença, J. T., & Efstathiou, S. (2012). The molecular basis of herpes simplex virus latency. FEMS microbiology reviews, 36(3), 684-705.
[2] Murphy, M. J., Fani, L., Ikram, M. K., Ghanbari, M., & Ikram, M. A. (2021). Herpes simplex virus 1 and the risk of dementia: a population-based study. Scientific Reports, 11(1), 8691.
[3] Wainberg, M., Luquez, T., Koelle, D. M., Readhead, B., Johnston, C., Darvas, M., & Funk, C. C. (2021). The viral hypothesis: how herpesviruses may contribute to Alzheimer’s disease. Molecular psychiatry, 26(10), 5476-5480.
[4] Powell-Doherty, R. D., Abbott, A. R., Nelson, L. A., & Bertke, A. S. (2020). Amyloid-ß and p-tau anti-threat response to herpes simplex virus 1 infection in primary adult murine hippocampal neurons. Journal of virology, 94(9), e01874-19.
[5] Chen, G. F., Xu, T. H., Yan, Y., Zhou, Y. R., Jiang, Y., Melcher, K., & Xu, H. E. (2017). Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacologica Sinica, 38(9), 1205-1235.
[6] Mandelkow, E. M., & Mandelkow, E. (2012). Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harbor perspectives in medicine, 2(7), a006247.
[7] Chung, H. Y., Kim, D. H., Lee, E. K., Chung, K. W., Chung, S., Lee, B., … & Yu, B. P. (2019). Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging and disease, 10(2), 367.
[8] Ren, J. L., Pan, J. S., Lu, Y. P., Sun, P., & Han, J. (2009). Inflammatory signaling and cellular senescence. Cellular signalling, 21(3), 378-383.
[9] Biswas, S., Das, R., & Banerjee, E. R. (2017). Role of free radicals in human inflammatory diseases. Aims Biophysics, 4(4), 596-614.
[10] Zhou, L., Ge, M., Zhang, Y., Wu, X., Leng, M., Gan, C., … & Dong, B. (2022). Centenarians alleviate inflammaging by changing the ratio and secretory phenotypes of T helper 17 and regulatory T cells. Frontiers in Pharmacology, 13, 877709.
