Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1
Abstract
Neurofibrillary tangles are one of the main neuropathological features of Alzheimer's disease (AD) and are composed of abnormally phosphorylated forms of a microtubule-associated protein called tau. What causes this abnormal phosphorylation is unknown. Our previous studies have implicated herpes simplex virus type 1 (HSV1) as an etiological agent in AD, and so we investigated whether infection with this virus induces AD-like tau phosphorylation. Here we demonstrate that HSV1 causes tau phosphorylation at several sites, including serine 202, threonine 212, serine 214, serine 396 and serine 404. In addition, we have elucidated the mechanism involved by showing that the virus induces glycogen synthase kinase 3beta and protein kinase A, the enzymes that cause phosphorylation at these sites. Our data clearly reveal the importance of HSV1 in AD-type tau phosphorylation, and support the case that the virus is a cause of the disease. Together with our previous data, our results point to the use of antiviral agents to slow the progression of the disease.
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Several studies have shown that tau hyperphosphorylation and intracerebral propagation can be caused by HSV-1.
“Moreover, several studies have also shown that tau hyperphosphorylation and intracerebral propagation can be caused by HSV-1 [48,49].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [49]
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What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
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- Authors
- Wozniak, M. A., Frost, A. L., & Itzhaki, R. F.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Itzhaki, Ruth F.
- ORCID
- Itzhaki, Ruth F.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2009-02-16
- Volume
- 16
- Issue
- 2
- Pages
- 341-350
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1807251344
- Cited by
- 216
- References
- 1
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 14 · 2023: 15 · 2022: 26 · 2021: 21 · 2020: 20 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 10
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- University of Manchester
- Henry Smith Charity
- Biotechnology and Biological Sciences Research Council
- 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
- Alzheimer's disease, tau phosphorylation
- MeSH terms
- Enzyme-Linked Immunosorbent Assay, Humans, Infections, Neuroblastoma, Phosphorylation, Serine, Threonine, tau Proteins, Herpesvirus 1, Human, Glycogen Synthase Kinase 3, Cell Line, Tumor
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