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Diagnostics Biochemistry and molecular biology, Microbiology and immunology, Neurology

Lying in Wait

Brain atrophy cannot be reversed, only slowed. For decades, scientists have grappled with diagnosing Alzheimer’s disease in its earliest stages to help patients delay progression as effectively as possible – a challenge exacerbated by the fact that there is no single cause of the disease. Most patients still only receive a diagnosis of “probable” Alzheimer’s because definitive identification of the disease requires examining post-mortem brain tissue for neurofibrillary tangles and amyloid plaques. As a result, a better understanding of the condition’s causes and risk factors is vital.

Varicella zoster virus (VZV), a form of herpesvirus that causes chickenpox, can reactivate later in life to cause shingles, whose symptoms include painful blisters and nodules in the skin. Previous evidence has demonstrated a link between herpes simplex virus (HSV) and increased risk of Alzheimer’s disease (1,2); however, it only seems to occur when the virus has reactivated to cause inflammatory conditions. Despite the established link between HSV and Alzheimer’s disease and evidence of VZV’s potential role, the sequence of events remains elusive.

To understand more, researchers at Tufts University and the University of Oxford infected human-induced neural stem cell cultures with HSV-1 and/or VZV and measured the presence of amyloid-β (Aβ), P-tau accumulation, neuroinflammation, and gliosis – all characteristic phenotypes of Alzheimer’s disease (3). They found that the main Alzheimer’s phenotypes caused by HSV-1 – Aβ and P-tau accumulation – were not present in VZV-infected cells, but gliosis and enhanced levels of proinflammatory cytokines were. This suggests an indirect impact of VZV on Alzheimer’s disease. Surprisingly, they found that infecting dormant HSV-1-infected cells with VZV led to HSV-1 reactivation and triggered other Alzheimer’s-like changes, such as Aβ and P-tau accumulation.

The results support the hypothesis that shingles can reactivate dormant HSV-1 in the brain, which then causes inflammation and the accumulation of proteins associated with Alzheimer’s disease.  First author Dana Cairns highlighted, “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” (4).

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  1. DM Cairns et al., “A 3D human brain-like tissue model of herpes-induced Alzheimer’s disease,” Sci Adv, 6, eaay8828 (2020). PMID: 32494701.
  2. RF Itzhaki, “Overwhelming evidence for a major role for herpes simplex virus type 1 (HSV1) in Alzheimer’s disease (AD); underwhelming evidence against,” Vaccines (Basel), 9, 679 (2021). PMID: 34205498.
  3. DM Cairns et al., “Potential involvement of varicella zoster virus in Alzheimer’s disease via reactivation of quiescent herpes simplex virus type 1,” J Alzheimers Dis, 88, 1189 (2022). PMID: 35754275.
  4. M Silver, “Common Viruses May Be Triggering the Onset of Alzheimer’s Disease” (2022). Available at:
About the Author
Liv Gaskill

During my undergraduate degree in psychology and Master’s in neuroimaging for clinical and cognitive neuroscience, I realized the tasks my classmates found tedious – writing essays, editing, proofreading – were the ones that gave me the greatest satisfaction. I quickly gathered that rambling on about science in the bar wasn’t exactly riveting for my non-scientist friends, so my thoughts turned to a career in science writing. At Texere, I get to craft science into stories, interact with international experts, and engage with readers who love science just as much as I do.

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