30 August 2022

Herpesviruses and Alzheimer's

The combination of two "harmless" viral infections provokes Alzheimer's disease

"First-hand science"

The leading cause of senile dementia – Alzheimer's disease – usually begins unnoticed. In the first months and even years, this insidious disease can disguise itself as forgetfulness, common for the elderly. The reasons for its development are not very clear, but recently we managed to assemble another part of this puzzle, which turned out to be well-known viruses.

People are constantly in contact with a variety of viruses, including pathogens of the usual SARS. Many of them do not cause much harm, causing an easily occurring disease. However, others remain "dormant" in the cells of our body and can be activated under certain circumstances.

The latter include herpesviruses, for example, herpes simplex virus type 1 (HSV-1), the cause of the appearance of "colds" (ulcers). As well as the chickenpox virus, which causes "chickenpox" during primary infection, and shingles when reactivated from a latent state.

Both of these viruses are extremely widespread: HSV-1, according to WHO, infected almost half of the world's population – about 3.7 billion people under the age of 50! And more than 90% of adolescents are infected with the causative agent of chickenpox without vaccination.

It is known that both HSV-1 and chickenpox virus are associated with the development of Alzheimer's disease. Reactivation of HSV-1 in brain neurons leads to the accumulation of altered (tau- and beta-amyloid) proteins, which is a characteristic sign of this pathology. As for the chickenpox virus, it turned out that vaccination against it reduces the risk of Alzheimer's disease. It is assumed that when reactivated, this virus, like HSV-1, can cause this disease both directly, through brain damage, and indirectly – through the development of neuroinflammation.

Now researchers from Tufts University (USA) and Oxford University (UK) The effects of HSV-1 and chickenpox virus on cultured nerve cells grown in the form of brain organoids – three-dimensional formations resembling areas of brain tissue were studied.

It turned out that infection by the chickenpox virus itself does not lead to the formation of clusters of pathological proteins characteristic of Alzheimer's disease and does not disrupt the function of neurons. But if this virus infects neurons already infected with HSV-1 herpesvirus, this leads to reactivation of the latter and is accompanied by a sharp increase in the number of pathological tau- and beta-amyloid proteins.

An increase in the level of proinflammatory cytokines in cells infected only with chickenpox virus suggested that it is inflammation that serves as a trigger for the activation of "sleeping" HSV-1. The latter, in turn, increases inflammation, which eventually leads to the accumulation of plaques of pathological proteins and other damage to the nervous tissue.

Thus, consecutive infection with two common and fairly harmless viruses can provoke Alzheimer's disease. It is possible that such effects can be caused by combined infection with other infections, including COVID-19, as well as the effects of such effects on the brain as head trauma or excessive alcohol consumption. 

Article by Cairns et al. Potential Involvement of Varicella Zoster Virus in Alzheimer's Disease via Reactivation of Quiescent Herpes Simplex Virus Type 1 is published in the Journal of Alzheimer's Disease.

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