Talking about the cause of Alzheimer’s disease is often frustrating and opaque. Much is about risk factors, not about biological mechanisms.
We’re told that the risk of developing Alzheimer’s disease increases with age, usually 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 disease in their 30s and 40s.
A head injury or a life of excessive drinking or high blood pressure or a vitamin D deficiency could all potentially predispose anyone.
You often read that Alzheimer’s disease is caused by those neurofibrillary or tau tangles that starve the brain of nutrients, and those sticky beta-amyloid plaques that clog the connection points between nerve cells.
Okay, but what’s the cause? them?
Researchers at Tufts University and the University of Oxford have come up with one answer: building on an idea that’s been halfway around for more than 20 years.
Using a 3D model of human tissue culture that mimics the brain, the researchers showed that the varicella zoster virus (VZV), which commonly causes chickenpox and shingles, herpes simplex (HSV1), the common virus that causes cold sores, can activate. the early stages of Alzheimer’s disease.
As the authors explain, HSV-1 lies dormant in 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 ‘characteristic features’ found in patients with Alzheimer’s disease – but a 2021 population 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 several, leading to Alzheimer’s disease.
A ‘brain’ made of silk
“Our results suggest one pathway to Alzheimer’s disease, caused by a VZV infection that creates inflammatory triggers that awaken HSV in the brain,” says Dr. Dana Cairns, a research associate in Tufts’ Department of Biomedical Engineering.
“While we have shown a link between VZV and HSV-1 activation, it is possible that other inflammatory events in the brain may also trigger HSV-1 and lead to Alzheimer’s disease.”
The experiment served as an investigation into the cause-and-effect relationship between the viruses and Alzheimer’s disease.
To do this, they created “brain-like environments” in tiny six-millimeter-wide donut-shaped sponges made of silk protein and collagen.
The sponges were populated with neural stem cells “which grow and become functional neurons capable of relaying signals to each other in a network, just as they do in the brain.”
Some stem cells also form glial cells that serve to keep the neurons alive, functioning and in place.
The researchers found that neurons grown in brain tissue could have been infected with VZV, “but that alone did not lead to the formation of the signature Alzheimer’s proteins tau and beta-amyloid.”
‘Neuronal signals are starting to slow down’
In fact, the neurons continued to function normally.
However, if the neurons were harboring HSV-1 while dormant, “exposure to VZV led to a reactivation of HSV and a dramatic increase in tau and beta-amyloid proteins, and neuronal signals began to slow down.”
dr. Cairns described the process as “a one-two punch”.
Crucially, the link between HSV-1 and Alzheimer’s disease “occurs only when HSV-1 is reactivated to cause ulcers, blisters, and other painful inflammatory conditions.”
The researchers suggest that “repeating cycles” of HSV-1 activation may lead to increased inflammation in the brain, plaque production and accumulation of neuronal and cognitive damage.
And the disease progresses from there.