Could viruses contain a cure for Alzheimer's disease?

Andre Bijernat

BBC News, Brazil

For decades, Professor Ruth Itzaki has studied the potential causes and treatments for Alzheimer's disease, seeking progress in the fight against this debilitating condition that affects an estimated 57 million people worldwide.

This brain disease – which is a form of dementia – robs individuals of their memory and, gradually, their identity.

Professor Itzaki, from the University of Manchester in the UK, was one of the first neuroscientists to suspect – and show – that common viruses might play a role in the development of Alzheimer's disease.

But it wasn't easy.

"Our scientific papers could not be accepted and published in scientific journals. As a result, we did not have access to funding for new research. And without enough money, it was difficult to continue our studies," says Professor Itzaki, who currently also works at the Institute of Population Ageing at the University of Oxford.

Professor Itzaki believes that if her work and that of other researchers had received more attention back then, there would be a better understanding today of the causes of dementia and the best ways to combat it.

That trend, however, has now begun to change.

In the past four years, the first clinical trials of vaccines and antiviral drugs – typically used to treat viral infections – as potential tools to prevent Alzheimer's disease have begun.

The role of inflammation

Thirty years ago, the amyloid cascade hypothesis began to gain traction as the main explanation for Alzheimer's disease.

Inflammation of the brain triggers the buildup of a protein called beta-amyloid.

This forms a cloudy plaque, or clumps, and begins to interfere with communication between neurons, or nerve cells, there.

Another type of protein that can be found in the brain – Tau – is also compromised by this buildup and begins to tangle inside nerve cells.

Tau protein normally helps neurons maintain their shape so they can efficiently transmit messages and communicate with each other.

Collectively, the buildup of plaque and the tangled protein Tau disables nerve cells and thus brain function.

This causes the death of neurons – resulting in progressive memory loss, difficulty with judgment, mood swings and other symptoms of Alzheimer's disease.

"But we still don't know what ultimately causes the deposition of these two proteins in the brain," adds neurologist Roberta Dill Rodríguez, a researcher at the School of Medicine at the University of São Paulo (FMUSP).

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Can viruses cause dementia?

It is common knowledge today that viruses can lie dormant in the body before being reactivated.

Forty years ago, Professor Itzaki began conducting the first studies of the genetic makeup of herpes simplex virus type 1 in the human brain.

This is an extremely common virus and causes cold sores on the lips.

It affects about 70 percent of the population.

These pioneering studies were the first to find this virus in the brain – until then, the central nervous system was believed to be a region protected from these viruses.

"We then began to speculate whether herpes reactivation throughout life could trigger a cascade of events that would culminate in damage to nervous system cells, ultimately leading to the death of those cells," says Professor Itzaki.

At the time, researchers were surprised to find that herpes was present in the brains of both people diagnosed with Alzheimer's disease and people who had never had the disease.

This led scientists to conclude that there must be other factors, such as genetics, that could explain why some individuals with the virus developed dementia and others did not.

In the 1990s, a team led by Professor Itzaki observed in the laboratory that the herpes simplex virus tends to concentrate in regions of the brain where large amounts of the protein beta-amyloid are deposited.

This led to a new theory: what if the nervous system produces this protein as a defense, with the goal of capturing the virus and inactivating it?

These molecules are known to be sticky in nature — and can grab onto the virus and make it harder for it to replicate before a more complex immune response is triggered.

However, because the herpes virus can remain latent and reactivate throughout life, it could cause inflammation in the brain and therefore trigger repeated production of beta-amyloid.

Over time, the theory goes, what once functioned as a protective mechanism becomes a problem, as the protein begins to damage the neurons themselves and eventually causes them to die.

The role of vaccines

So what can be done to prevent this?

The Welsh Government launched a shingles vaccination campaign in 2013, but set out very clear parameters.

Herpes zoster is caused by the reactivation of the varicella-zoster virus and is characterized by a painful skin rash.

Only people born between September 2, 1933 and September 1, 1934 were eligible to receive this vaccine.

"We had a situation very similar to a clinical trial: two groups that are very similar in many ways, that can be compared, and the only difference is their eligibility to receive the herpes zoster vaccine," said Professor Pascal Geldsetzer, from the Department of Medicine, Epidemiology and Population Health at Stanford University in the US.

The results of the analysis showed that, among people who received the vaccine, the likelihood of being diagnosed with dementia over the next seven years was 3,5 percent lower than average – a rate considered significant.

"Our study showed that this protective effect is large and surpasses the pharmacological tools currently available for the treatment of dementia," says Professor Geldscher.

But what explains this effect?

"A growing body of evidence suggests that viruses that can preferentially behave in the nervous system and remain there for most of life may be involved in the onset of dementia," says Professor Geldsetzer.

In this sense, vaccination against herpes zoster blocked viral reactivation and therefore prevented the infectious agent from serving as a trigger for inflammation and beta-amyloid production.

Professor Geldsecer adds: "We have increasing evidence that vaccines produce effects on the immune system that are much broader than simply stimulating the production of antibodies against a specific pathogen. And this broader immunological effect, in turn, can provide benefits against other diseases."

The author of the newly published scientific paper now wants to conduct a conventional clinical trial – which involves recruiting volunteers, dividing them into groups, and assessing the effects of a vaccination against dementia over a period of time.

"If the herpes zoster vaccine can actually prevent or delay the onset of dementia, that would be a huge discovery," he says.

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