THE HERPES – ALZHEIMER’S CONNECTION
I wrote about Alzheimer’s disease in my post Exercise Might be the Best Medicine for Avoiding Alzheimer’s. I continually monitor what’s happening in Alzheimer’s studies and since then have discovered new research connecting herpes viruses—such as common cold sores—and dementia. The best news to us seniors is that these investigations are pointing to possible development of a vaccine to prevent or at least treat Alzheimer’s.
Here are excerpts from the July 12, 2018 TheAtlantic.com article Even More Evidence for the Link Between Alzheimer’s and Herpes
In 1907, the German psychiatrist Alois Alzheimer published a description of a 50-year-old woman who suffered from memory problems, hallucinations, and delusions. In the woman’s brain, Alzheimer noticed unusual lumps, or “plaques,” which “were caused by the deposition of an unusual substance.” Eight decades later, the mystery substance was finally identified as a protein called amyloid beta. Though small, it can accumulate in large clusters that are somehow toxic to neurons. Those harmful plaques are one of the hallmarks of the disease that bears Alzheimer’s name.
What amyloid beta normally does in the brain isn’t clear. Robert Moir, a neurologist at the MassGeneral Institute for Neurodegenerative Disease, says that many researchers have cast it as a villainous molecule with no beneficial function. “It’s just bad, bad, bad,” he says. “But it has become increasingly obvious that this isn’t true.” Moir thinks that amyloid beta has a more heroic role, as a foot soldier of our immune system. It protects neurons from infectious microbes—and from herpes viruses, in particular.
William Eimer, a member of Moir’s team, demonstrated this protection by injecting the common herpes virus HSV–1 into the brains of two kinds of mice: normal rodents and ones that were genetically engineered to produce high levels of amyloid beta in their brains. The latter were better at resisting the viruses. Eimer then got similar results when he injected a different herpes virus, HHV–6, into human cells growing in a dish
Amyloid beta protects against these viruses by latching onto them in large numbers, imprisoning them in self-assembling cages. That’s typically a good thing, but Moir argues that if the process goes on for too long, it builds up to the problematic plaques of Alzheimer’s. According to him, amyloid beta is still at the heart of the Alzheimer’s story, but it isn’t the villain. “In our model, Alzheimer’s is caused by amyloid beta’s reaction to something else, and most likely some kind of infection” like herpes, he says.
Moir notes that amyloid beta also exists in most other backboned animals. The protein first evolved around 400 million years ago, which is also roughly when the herpes virus family first appeared on the scene. “It’s clear that herpes and amyloid beta have been slugging it out since before there were insects,” Moir says. “One’s tuned to escape and the other to capture.”
This gives credence to the long-dismissed idea that viruses—and herpes, in particular—are involved in Alzheimer’s in some way.
And here are excerpts from the October 19, 2018 article in Science Daily Does herpes cause Alzheimer’s?
What causes Alzheimer’s disease? The answer could be right under our noses, says leading expert Professor Ruth Itzhaki. Her latest paper presents a lifetime of research evidence that the herpes virus responsible for cold sores can also cause Alzheimer’s — and new data which show antiviral drugs drastically reduce risk of senile dementia in patients with severe herpes infections. The review in Frontiers in Ageing Neuroscience raises the tantalizing prospect of a simple, effective preventive treatment for one of humanity’s costliest disorders.
The HSV1 theory of Alzheimer’s disease
Herpes viruses are the dreaded ‘gift that keeps on giving’. They remain lifelong in our neurons and immune cells, reactivating and resurfacing in characteristic blisters when we’re run down by stress or illness. Herpes Simplex Virus 1 (HSV1) infects most people by the time they reach old age
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 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 increased risk of Alzheimer’s. [A hypothesis currently gaining widespread support is that the ApoE gene—in a direct protein-protein interaction—is involved in the deposition of amyloid beta (Alzheimer’s plaques).]
“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 development of Alzheimer’s.”
Proving the theory
Few countries collect the population data required to test this theory — for example, to find out whether antiviral treatments reduce dementia risk.
In Taiwan however, researchers have done just that. There, 99.9% of the population is enrolled in a National Health Insurance Research Database, which is 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 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.”
Towards a cure
“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 usage of antiherpes antivirals — which are safe and well-tolerated — to treat Alzheimer’s disease.
“They also incentivize development of an HSV1 vaccine, which would likely be the most effective treatment.”
And wouldn’t that be terrific!