Life Wellbeing How two common viruses trigger the early stages of Alzheimer’s disease

How two common viruses trigger the early stages of Alzheimer’s disease

Researchers have described a biological mechanism for developing Alzheimer's disease. Photo: Getty
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Talk about what causes Alzheimer’s disease tends to be frustrating and opaque. A lot of it is about risk factors, not biological mechanisms.

We’re told that the risk for developing Alzheimer’s increases with age, mostly after we hit 65. Women are at greater risk than men. People with a family history of the disease are more likely to get it themselves.

People with Down Syndrome become vulnerable to Alzheimer’s in their 30s and 40s.

A head injury or a life of excessive drinking or high blood pressure or a vitamin D deficiency are all said to possibly make one prone.

Often, you’ll read that Alzheimer’s is caused by those neurofibrillary or tau tangles that starve the brain of nutrients, and those sticky beta-amyloid plaques that clog up the connecting points between nerve cells.

Okay, but what causes them?

Researchers from Tufts University and the University of Oxford have come up with one answer – building on an idea that’s been half formed for more than 20 years.

Using a 3D human tissue culture model that mimics the brain, the researchers demonstrated that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV1), the common virus that causes cold sores, to set in train the early stages of Alzheimer’s disease.

As the authors explain it, HSV-1 lies dormant within the neurons of the brain, “but when activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function”.

These are ‘signature features’ found in patients with Alzheimer’s – but a 2021 population-based study suggested that while HSV-1 can cause cognitive decline, it doesn’t cause dementia.

The Oxford/Tufts scientists argue that their experiments have in fact shown how the relationship between these two viruses serves as one pathway, perhaps of several, leading to Alzheimer’s.

A ‘brain’ made of silk

“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain,” said Dr Dana Cairns, a research associate in Tufts’ Biomedical Engineering Department.

“While we demonstrated a link between VZV and HSV-1 activation, it’s possible that other inflammatory events in the brain could also awaken HSV-1 and lead to Alzheimer’s disease.”

The experiment served as an investigation of the cause-and-effect relationship between the viruses and Alzheimer’s disease.

For this, they created “brain-like environments” in small six millimetre-wide donut-shaped sponges made of silk protein and collagen.

The sponges were populated with neural stem cells “that grow and become functional neurons capable of passing signals to each other in a network, just as they do in the brain”.

Some of the stem cells also form glial cells which serve to keep the neurons alive, functioning and in place.

The researchers found that neurons grown in the brain tissue could be infected with VZV, “but that alone did not lead to the formation of the signature Alzheimer’s proteins tau and beta-amyloid”.

‘Neuronal signals begin to slow’

In fact the neurons continued to function normally.

However, if the neurons already harboured dormant HSV-1, “the exposure to VZV led to a reactivation of HSV, and a dramatic increase in tau and beta-amyloid proteins, and the neuronal signals begin to slow down”.

Dr Cairns described the process as “a one-two punch”.

Crucially, the link between HSV-1 and Alzheimer’s disease “only occurs when HSV-1 has been reactivated to cause sores, blisters, and other painful inflammatory conditions”.

The researchers suggest that “repeat cycles” of HSV-1 activation can lead to more inflammation in the brain, production of plaques, and accumulation of neuronal and cognitive damage.

And the disease progresses from there.