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Cited by 16Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Aβ plaques do not protect against HSV‐1 infection in a mouse model of familial Alzheimer's disease, and HSV‐1 does not induce Aβ pathology in a model of late onset Alzheimer's disease

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Bocharova, Olga V., Fisher, Aidan, Pandit, Narayan P., Molesworth, Kara, Mychko, Olga, Scott, Alison J., Makarava, Natallia, Ritzel, Rodney +1 more·2023·Brain Pathology
DOI 10.1111/bpa.13116PMC PMC9836376
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Abstract

The possibility that the etiology of late onset Alzheimer's disease is linked to viral infections of the CNS has been actively debated in recent years. According to the antiviral protection hypothesis, viral pathogens trigger aggregation of Aβ peptides that are produced as a defense mechanism in response to infection to entrap and neutralize pathogens. To test the causative relationship between viral infection and Aβ aggregation, the current study examined whether Aβ plaques protect the mouse brain against Herpes Simplex Virus 1 (HSV‐1) infection introduced via a physiological route and whether HSV‐1 infection triggers formation of Aβ plaques in a mouse model of late‐onset AD that does not develop Aβ pathology spontaneously. In aged 5XFAD mice infected via eye scarification, high density of Aβ aggregates did not improve survival time or rate when compared with wild type controls. In 5XFADs, viral replication sites were found in brain areas with a high density of extracellular Aβ deposits, however, no association between HSV‐1 and Aβ aggregates could be found. To test whether HSV‐1 triggers Aβ aggregation in a mouse model that lacks spontaneous Aβ pathology, 13‐month‐old hAβ/APOE4/Trem2*R47H mice were infected with HSV‐1 via eye scarification with the McKrae HSV‐1 strain, intracranial inoculation with McKrae, intracranial inoculation after priming with LPS for 6 weeks, or intracranial inoculation with high doses of McKrae or 17syn + strains that represent different degrees of neurovirulence. No signs of Aβ aggregation were found in any of the experimental groups. Instead, extensive infiltration of peripheral leukocytes was observed during the acute stage of HSV‐1 infection, and phagocytic activity of myeloid cells was identified as the primary defense mechanism against HSV‐1. The current results argue against a direct causative relationship between HSV‐1 infection and Aβ pathology.

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  • Numerous viral and bacterial agents, including herpesviruses, flaviviruses, HIV, hepatitis viruses, Borna virus, Ljungan virus, and influenza A virus, have been linked to an increased risk of Alzheimer's disease.

    “Since then, numerous viral and bacterial agents, including herpesviruses, flaviviruses, human immunodeficiency virus (HIV), hepatitis viruses, Borna virus, Ljungan virus, and influenza A virus, have been linked to an increased risk of AD [163].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [163]

    The Introduction and Discussion (pages unavailable) describe herpesviruses as pathogens linked to late-onset Alzheimer’s disease, while noting that the association is controversial. The paper does not identify flaviviruses, HIV, hepatitis viruses, Borna virus, Ljungan virus, or influenza A virus as linked to increased Alzheimer’s risk, so it supports only part of the cited list. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Bocharova, O. V., Fisher, A., Pandit, N. P., Molesworth, K., Mychko, O., Scott, A. J., Makarava, N., Ritzel, R., & Baskakov, I. V.
Affiliations
University of Maryland, Baltimore (US)
Corresponding author
Baskakov, Ilia V.
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2022-09-05
Volume
33
Issue
1
Pages
e13116-e13116
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/bpa.13116
PMC
PMC9836376
OpenAlex
W4294983507
Cited by
16
References
10
Citations by year
2026: 5 · 2025: 2 · 2024: 6 · 2023: 3
FWCI
1.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Pathology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • Infectious Diseases Society of America
  • IDSA Foundation
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, amyloid plaques, herpes simplex virus type 1, viral infection, 5xFAD mice, neurovirulence, neuroinflammation, late-onset Alzheimer's disease
MeSH terms
Alzheimer Disease, Animals, Brain, Disease Models, Animal, Herpes Simplex, Membrane Glycoproteins, Mice, Transgenic, Receptors, Immunologic, Amyloid beta-Peptides, Herpesvirus 1, Human, Mice

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