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Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model
Dana M. Cairns, Brooke M. Smiley, Jordan A. Smiley, Yasaman A Khorsandian, Marilyn F. Kelly, Ruth F. Itzhaki, David Lee Kaplan. Science Signaling, 2025-01-07
Topic: Brain proteins, microglia and lab models
-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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cairns, D. M., Smiley, B. M., Smiley, J. A., Khorsandian, Y. A., Kelly, M. F., Itzhaki, R. F., et al. (2025). Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model. Science Signaling. https://doi.org/10.1126/scisignal.ado6430
Vancouver
Cairns DM, Smiley BM, Smiley JA, Khorsandian YA, Kelly MF, Itzhaki RF, et al. Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model. Science Signaling. 2025. doi:10.1126/scisignal.ado6430. PMID: 39772530.
BibTeX
@article{cairns2025-39772530,
author = {Cairns, Dana M. and Smiley, Brooke M. and Smiley, Jordan A. and Khorsandian, Yasaman A and Kelly, Marilyn F. and Itzhaki, Ruth F. and Kaplan, David Lee},
title = {{Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model}},
journal = {Science Signaling},
year = {2025},
doi = {10.1126/scisignal.ado6430},
pmid = {39772530},
url = {https://doi.org/10.1126/scisignal.ado6430}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- 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.
Why it matters
In a human brain tissue model, repeated mild controlled blows reactivated latent HSV-1 and led to amyloid and phosphorylated tau accumulation and activated gliosis, effects that were absent in mock-infected tissue. This is a laboratory model, so it suggests a possible contributing mechanism but does not prove that preventing such injuries or infections prevents Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science Signaling) |
| Journal's citation record | 2 / 4 | Science Signaling: journal h-index 194 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 38 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 20.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 38 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David Lee Kaplan: h-index 198 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39772530) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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