What causes Alzheimer's disease? The answer might be right under our noses, says leading expert Professor Ruth Itzhaki. Her latest work presents life-long research that herpes virus, which is responsible for cold sores, can also cause Alzheimer's – and new data showing antiviral drugs dramatically reduce the risk of senile dementia in patients with severe herpes infections. The article in Frontiers in Aging Neuroscience presents the tantalizing prospect of simple, effective preventative treatment for one of humanity's most expensive diseases.
The HSV1 Theory of Alzheimer's Disease
Herpes Viruses They remain lifelong in our neurons and immune cells, reactivating and reappearing in characteristic blisters when we are exhausted from stress or illness Most people are infected with the herpes simplex virus 1
But what happens to infected neurons in our brain during this reactivation? "
" HSV1 could account for 50% or more of Alzheimer's disease cases, "says Professor Itzhaki, who over 25 years at the University of Manchester has worked to investigate a possible link.
HSV1 is better known as the cause of lip gloss Itzhaki has previously shown that cold sores are more common in carriers of APOE-ε4 – a gene variant that offers an increased risk of Alzheimer's disease.
"Our theory is that in APOE-ε4 carriers reactivation is more frequent or more detrimental to HSV1-infected brain cells, thereby accumulating damage that culminates in Alzheimer's development."
Proof of Theory  Few countries collect the population data needed to test this theory – for example, to find out if antiviral treatments reduce the risk of dementia
In Taiwan, researchers have done just that. There, 99.9% of the population is registered in a National Health Insurance Research Database, which is searching intensively for information about microbial infections and diseases. In 2017-2018, three studies were published that include Taiwanese data on the development of senile dementia – of which Alzheimer's is the major cause – and the treatment of patients with marked overt signs of infection with HSV or varicella-zoster virus (VZV)
"The striking findings include evidence that the risk of senile dementia is much greater in those infected with HSV, and that antiviral treatment with anti-herpes represents a dramatic decrease in the number of severely affected HSV1 dementia develops later on. "
Previous findings from Itzhaki's own research group provide a mechanistic context that supports these epidemiological findings. They found that HSV1 causes protein deposits that are characteristic of Alzheimer's: "plaques" between neurons and "entanglements" in them.
"Viral DNA is very specifically localized in plaques in the postmortem brain tissue of Alzheimer's patients, and the major proteins from both plaques and tangles also accumulate in HSV1-infected cell cultures – and antiviral drugs can prevent this."
"It should be emphasized that the results of these Taiwanese studies only apply to severe HSV1 (or VZV) infections, which are rare," Itzhaki admits. "Ideally, we would study dementia rates in people who have had mild HSV1 infection, including herpes labialis (cold sores) or mild genital herpes, but these are much less likely to be documented."
Although more work is needed to confirm this and to define a causal relationship between HSV1 infection and Alzheimer's disease, Itzhaki is excited about the treatment prospects.
"With more than 150 publications strongly supporting an HSV1 role in Alzheimer's, these Taiwan results justify the use of anti-herpes virostatics – safe and well-tolerated – for the treatment of Alzheimer's disease.
19659004] "They also provide an incentive to develop an HSV1 vaccine that is likely to be the most effective treatment."
This reflects the growing worldwide use of the human papillomavirus (HPV) vaccine to prevent cervical cancer – another Linkage between viruses and diseases that emerged in a similar research process.
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