Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques
Abstract
The brains of Alzheimer's disease sufferers are characterized by amyloid plaques and neurofibrillary tangles. However, the cause(s) of these features and those of the disease are unknown, in sporadic cases. We previously showed that herpes simplex virus type 1 is a strong risk factor for Alzheimer's disease when in the brains of possessors of the type 4 allele of the apolipoprotein E gene (APOE-epsilon4), and that beta-amyloid, the main component of plaques, accumulates in herpes simplex virus type 1-infected cell cultures and mouse brain. The present study aimed to elucidate the relationship of the virus to plaques by determining their proximity in human brain sections. We used in situ polymerase chain reaction to detect herpes simplex virus type 1 DNA, and immunohistochemistry or thioflavin S staining to detect amyloid plaques. We discovered a striking localization of herpes simplex virus type 1 DNA within plaques: in Alzheimer's disease brains, 90% of the plaques contained the viral DNA and 72% of the DNA was associated with plaques; in aged normal brains, which contain amyloid plaques at a lower frequency, 80% of plaques contained herpes simplex virus type 1 DNA but only 24% of the viral DNA was plaque-associated (p < 0.001). We suggest that this is because in aged normal individuals, there is a lesser production and/or greater removal of beta-amyloid (Abeta), so that less of the viral DNA is seen to be associated with Abeta in the brain. Our present data, together with o…
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CCNT2's use by HSV-1 is a plausible link to AD due to the hypothesis that HSV-1 can trigger amyloid plaques.
“This is a plausible link to AD due to the hypothesis that HSV-1 can trigger amyloid plaques [47, 48].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [48]
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“This idea fits with the findings that HSV1 and Borrelia DNA have been found in plaque cores of AD brains.(400,401) Aβ peptides are able to interact and entrap various bacterial strains and viruses, such as HSV1 and HSV6, block their entry into the host cells to replicate.”
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- Authors
- Wozniak, M., Mee, A., & Itzhaki, R.
- Affiliations
- University of Manchester (GB)
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2008-10-30
- Volume
- 217
- Issue
- 1
- Pages
- 131-138
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W2088177247
- Cited by
- 464
- References
- 0
- Citations by year
- 2026: 38 · 2025: 34 · 2024: 37 · 2023: 32 · 2022: 44 · 2021: 54 · 2020: 30 · 2019: 36 · 2018: 26 · 2017: 11 · 2016: 16 · 2015: 18 · 2014: 21 · 2013: 12 · 2012: 15
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Alzheimer Society
- Henry Smith Charity
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- herpes simplex virus type 1, Alzheimer's disease, amyloid plaques, amyloid-beta, viral DNA localization, APOE ε4, neurofibrillary tangles, antiviral therapy, vaccination
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, DNA, Viral, Female, Frontal Lobe, Herpes Simplex, Humans, Male, Temporal Lobe, Polymerase Chain Reaction, Herpesvirus 1, Human, Genetic Predisposition to Disease, Apolipoprotein E4, Plaque, Amyloid
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