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Cited by 89Alzheimer's disease research and treatmentsHerpesvirus Infections and TreatmentsNeuroinflammation and Neurodegeneration Mechanisms

Intracerebral propagation of Alzheimer’s disease: strengthening evidence of a herpes simplex virus etiology

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Ball, Melvyn J., Lukiw, Walter J., Kammerman, Eli M., Hill, James M.·2013·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2012.07.005PMC PMC3578985
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Abstract

Background: A faulty human protein, abnormally phosphorylated tau, was recently publicized to spread “like a virus” from neuron to neuron in Alzheimer's patients’ brains. For several decades, we have been amassing arguments showing that herpes simplex virus type 1 (HSV‐1), not p‐tau, propagates this interneuronal, transsynaptic pathologic cascade. Methods: We reiterate convincing data from our own (and other) laboratories, reviewing the first anatomic foothold neurofibrillary tangles gain in brainstem and/or entorhinal cortex; the chronic immunosurveillance cellularity of the trigeminal ganglia wherein HSV‐1 awakens from latency to reactivate; the inabilities of p‐tau protein's physical properties to promote it to jump synapses; the amino acid homology between human p‐tau and VP22, a key target for phosphorylation by HSV serine/threonine–protein kinase UL13; and the exosomic secretion of HSV‐1–infected cells’ L‐particles, attesting to the cell‐to‐cell passage of microRNAs of herpesviruses. Results: The now‐maturing construct that reactivated HSV‐1 best accounts for the intracerebral propagation of AD changes in the human brain should at last seem highly attractive. This hypothesis might even explain statins' apparent mechanism in some studies for lowering AD incidence. Conclusion: Provided that funding agencies will quickly ignite a new realm of investigation, the rejuvenated enthusiasm for testing this optimistic construct holds incalculable potential for rapid, efficacious clinical application, through already available and relatively safe antiviral therapeutics.

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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 [48]

    Section 4 reports studies in which HSV-1 infection increased tau phosphorylation in neuronal cells. The Abstract (Background) argues that HSV-1 propagates the pathological cascade, but section 5 presents its spread within the human brain as a hypothesis, not something studies have shown to cause intracerebral propagation of Alzheimer’s disease. (LLM, conf=0.84)

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Authors
Ball, M. J., Lukiw, W. J., Kammerman, E. M., & Hill, J. M.
Affiliations
  • Oregon Health & Science University (US)
  • Louisiana State University Health Sciences Center New Orleans (US)
  • Laguna Niguel CA USA
Corresponding author
Ball, Melvyn J.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2012-11-16
Volume
9
Issue
2
Pages
169-175
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2012.07.005
PMC
PMC3578985
OpenAlex
W2153988288
Cited by
89
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 10 · 2014: 17 · 2013: 5 · 2012: 1
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (R01‐EY006311, R01‐EY14289)
  • National Institute on Aging
  • National Institutes of Health (AG18031, AG038834)
  • Research to Prevent Blindness
  • Louisiana Board of Regents
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, herpes simplex virus type 1
MeSH terms
Alzheimer Disease, Animals, Brain, Herpes Simplex, Humans, tau Proteins, Simplexvirus

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