Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model, 2025, Dana M. Cairns

[Mij]

Editor’s summary
Infection with herpes simplex virus type 1 (HSV-1) is common, lifelong, and often in a latent state with periodic reactivation. It is a risk factor for neurodegenerative disease and dementia in some individuals, as are repeated head injuries like concussions. Cairns et al. found that latent HSV-1 was reactivated by repeated mechanical injury to mimic concussions in a three-dimensional human brain tissue model. This mechanism triggered the aggregation of β amyloid and other pathological features associated with neurodegenerative diseases in a manner dependent on the inflammatory cytokine IL-1β. The findings directly link two risk factors in a mechanism that may contribute to dementia-related disease.

Abstract
Infection with herpes simplex virus type 1 (HSV-1) in the brains of APOE4 carriers increases the risk of Alzheimer’s disease (AD). We previously found that latent HSV-1 in a three-dimensional in vitro model of APOE4-heterozygous human brain tissue was reactivated in response to neuroinflammation caused by exposure to other pathogens. Because traumatic brain injury also causes neuroinflammation, we surmised that brain injury might similarly reactivate latent HSV-1.

Here, we examined the effects of one or more controlled blows to our human brain model in the absence or presence of latent HSV-1 infection. After repeated, mild controlled blows, latently infected tissues showed reactivation of HSV-1; the production and accumulation of β amyloid and phosphorylated tau (which promotes synaptic dysfunction and neurodegeneration); and activated gliosis, which is associated with destructive neuroinflammation. These effects are collectively associated with AD, dementia, and chronic traumatic encephalopathy (CTE) and were increased with additional injury but were absent in mock-infected tissue. Blocking the cytokine IL-1β prevented the induction of amyloid and gliosis in latently infected monolayer cultures after scratch wounding.

We thus propose that after repeated mechanical injuries to the brain, such as from direct blows to the head or jarring motions of the head, the resulting reactivation of HSV-1 in the brain may contribute to the development of AD and related diseases in some individuals.
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[Sly Saint]

'Reanimated' herpes viruses lurking in the brain may link concussions and dementia

Inflammation can reawaken dormant viruses in the brain, which may help to explain why concussions often precede dementia, a new study finds.

Brain injuries like concussions raise the risk of dementia, and the more blows someone takes to the head, the higher that risk becomes, evidence suggests. Scientists are investigating what happens in the brain after injury that might lead to changes tied to dementia — for instance, a buildup of abnormal proteins and the malfunction and death of brain cells. Such changes are seen in Alzheimer's disease and chronic traumatic encephalopathy (CTE), a disorder that's recently gained recognition in high-impact sports.

Some scientists think these changes may be linked to a common virus: herpes simplex virus 1 (HSV-1), the germ behind cold sores.

Herpesviruses — a broader group that also includes the viruses behind chickenpox and mono — have an ability to go dormant in the body and then later reactivate. "They can remain latent in your body forever," said lead study author Dana Cairns, a postdoctoral research fellow at Tufts University. There's evidence that HSV-1 can somehow weasel its way into the brain and then lie there in wait, Cairns told Live Science.

What's new here is that the researchers have demonstrated that physical injury can activate latent viruses in the brain, said Dr. Gorazd Stokin, who leads a neuroscience lab at the Institute of Molecular and Translational Medicine in the Czech Republic and was not involved in the new study.

The new research relied on miniature laboratory models of the brain, so more work will be needed to show that the results are relevant to people. "But it's a good first step to show something interesting," said Stokin, who is also a consultant neurologist at the Gloucestershire Hospitals NHS Foundation Trust in the U.K.

Viruses in dementia
The idea of viruses sparking dementia isn't new; Ruth Itzhaki, a co-author of the new paper, raised the notion in 1991. Itzhaki and colleagues had found the virus in the brains of older adults who had died of Alzheimer's.

'Reanimated' herpes viruses lurking in the brain may link concussions and dementia