New York: An international team of researchers has found that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer’s disease.
Alzheimer’s disease can begin almost imperceptibly, often masquerading in the early months or years as forgetfulness that is common in older age. What causes the disease remains largely a mystery.
To explore, the team from Tufts University in the US and the University of Oxford in the UK used a three-dimensional human tissue culture model mimicking the brain.
They found that normally HSV-1 — one of the main variants of the HSV virus — lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function — signature features found in patients with Alzheimer’s.
“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 Dana Cairns, a research associate in the Biomedical Engineering Department at Tufts.
The study, published in the Journal of Alzheimer’s Disease, showed 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.
To better understand the cause-and-effect relationship between the viruses and Alzheimer’s disease, the researchers re-created brain-like environments in small 6 millimetre-wide donut-shaped sponges made of silk protein and collagen.
They populated the sponges 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 are typically found in the brain and help keep the neurons alive and functioning.
The researchers found that neurons grown in the brain tissue can be infected with VZV, but that alone did not lead to the formation of the signature Alzheimer’s proteins tau and beta-amyloid the components of the tangled mess of fibres and plaques that form in Alzheimer’s patients’ brains — and that the neurons continued to function normally.
However, if the neurons already harboured quiescent 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.
“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” said Cairns.
“It’s still possible that other infections and other pathways of cause and effect could lead to Alzheimer’s disease, and risk factors such as head trauma, obesity, or alcohol consumption suggest they may intersect at the re-emergence of HSV in the brain,” she added.