The Link Between Alzheimer Disease and Herpes Simplex Virus Infection: Better Late Than Never, or Better Never Than Late?
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Other herpesviruses, including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6, have been implicated in Alzheimer's disease, and HHV6 promotes Aβ plaque formation.
“Other herpesviruses, including cytomegalovirus, Epstein–Barr virus, and human herpesvirus 6 (HHV6), have also been implicated [166]. Notably, HHV6 promotes Aβ plaque formation, highlighting the broader contribution of this viral family to amyloidogenic processes [166].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [166]
The main text (page unavailable) reports an overabundance of HHV-6A and HHV-7 transcripts in Alzheimer’s brain, supporting the implication of HHV-6. It does not implicate cytomegalovirus or Epstein–Barr virus. Its discussion of enhanced Aβ accumulation and plaque generation concerns HSV-1, not HHV-6, so it does not support the claim that HHV-6 promotes plaque formation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCarriers of the APOE4 allele show a synergistic increase in Alzheimer's disease likelihood when infected with HSV-1, suggesting that viral infection and host genotype interact to modulate disease trajectory.
“Carriers of the APOE4 allele show a synergistic increase in AD likelihood when infected with HSV-1, suggesting that viral infection and host genotype interact to modulate disease trajectory [166].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [166]
The main text (page not supplied) reports a much higher odds ratio for APOE-E4 among HSV-1-PCR-positive AD cases than among PCR-negative AD cases, supporting a possible interaction. But it describes the mechanism as proposed and says the APOE-E4/HSV-1 brain-DNA association has not been consistently replicated. The claim overstates this qualified evidence as a demonstrated synergistic increase in AD likelihood for carriers infected with HSV-1. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHSV-1 establishes latency in the trigeminal ganglia, can reactivate and invade the central nervous system under conditions such as aging or immunosuppression, and its cycles of latency and reactivation align with the progressive nature of Alzheimer's disease.
“HSV-1, which establishes latency in the trigeminal ganglia, can reactivate and invade the central nervous system under conditions such as aging or immunosuppression. Cycles of latency and reactivation align with the progressive nature of AD, potentially contributing to recurrent inflammatory insults and cumulative neuronal damage [166].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [166]
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Cites
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Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
- Authors
- Tyler, K. L.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Tyler, Kenneth L.
- ORCID
- Tyler, Kenneth L.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 18
- Issue
- 4
- Pages
- 2421-2424
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC8804014
- OpenAlex
- W3196768278
- Cited by
- 5
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 0.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- Alzheimer's disease, herpes simplex virus, viral infection, neurodegeneration
- MeSH terms
- Alzheimer Disease, Herpes Simplex, Humans, Herpesvirus 1, Human
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