Antivirals may be prospective treatment for Alzheimer's disease

Herpes simplex virus type 1 (HSV1) may be associated with the development of Alzheimer's disease (AD), according to a new study.

The review, published in the journal Frontiers in Ageing Neuroscience, further adds that antiviral drugs drastically reduce the risk of senile dementia in patients with severe herpes infections. The findings are significant as it raises the prospects of a simple, effective preventive treatment for one of humanity's costliest disorders.

Ruth Itzhaki, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, conducted the study to investigate if HSV1 is a major risk for Alzheimer’s disease.

Association between HSV1 and Alzheimer's disease

Herpes virus remains lifelong in the neurons and immune cells, reactivating and resurfacing in characteristic blisters during stress or illness. Most people are infected by HSV1 by the time they reach old age.

"HSV1 could account for 50% or more of Alzheimer's disease cases," says Professor Itzhaki, who has spent over 25 years at the University of Manchester investigating a potential link.

HSV1 is better known as the cause of cold sores. Itzhaki has shown previously that cold sores occur more frequently in carriers of APOE-ε4 - a gene variant that confers an increased risk of Alzheimer's.

"Our theory is that in APOE-ε4 carriers, reactivation is more frequent or more harmful in HSV1-infected brain cells, which as a result accumulate damage that culminates in the development of Alzheimer's."

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Studies demonstrating the association

In Taiwan, the researchers have collected the data required to test the theory -- whether antiviral treatments reduce the risk of dementia. For which, National Health Insurance Research Database -- in which about 99.9% of the population is enrolled -- was being extensively mined for information on microbial infections and disease. In 2017-2018 three studies were published describing Taiwanese data on the development of senile dementia - of which Alzheimer's is the main cause - and the treatment of patients with marked overt signs of infection with HSV or varicella-zoster virus (VZV, the chickenpox virus).

"The striking results include evidence that the risk of senile dementia is much greater in those who are infected with HSV, and that anti-herpes antiviral treatment causes a dramatic decrease in the number of those subjects severely affected by HSV1 who later develop dementia."

Previous findings from Itzhaki's own research group provide a mechanistic link which supports these epidemiological findings. They found that HSV1 causes protein deposits characteristic of Alzheimer's: 'plaques' between neurons, and 'tangles' inside of them.

"Viral DNA is located very specifically within plaques in postmortem brain tissue from Alzheimer's sufferers. The main proteins of both plaques and tangles accumulate also in HSV1-infected cell cultures - and antiviral drugs can prevent this."

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Treatment prospects for Alzheimer's disease

"It should be stressed that the results of these Taiwanese studies apply only to severe HSV1 (or VZV) infections, which are rare," admits Itzhaki. "Ideally, we would study dementia rates amongst people who have suffered mild HSV1 infection, including herpes labialis (cold sores) or mild genital herpes, but these are far less likely to be documented."

Although further work is needed to confirm and define a causal link between HSV1 infection and Alzheimer's, Itzhaki is enthusiastic about the treatment prospects.

"Considering that over 150 publications strongly support an HSV1 role in Alzheimer's, these Taiwan findings greatly justify the usage of antiherpes antivirals - which are safe and well-tolerated - to treat Alzheimer's disease.

"They also incentivize the development of an HSV1 vaccine, which would likely be the most effective treatment."

For further reference follow the link: https://doi.org/10.3389/fnagi.2018.00324