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Cited by 24Alzheimer's disease research and treatmentsViral-associated cancers and disordersCytomegalovirus and herpesvirus research

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

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Romanescu, Constantin, Schreiner, Thomas Gabriel, Mukovozov, Ilya·2022·Journal of Clinical Medicine
DOI 10.3390/jcm11113061PMC PMC9181317
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Abstract

Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the pursuit of a better understanding of disease mechanisms; however, the ultimate goal of obtaining a viable treatment option remains elusive. Neurodegenerative disease as an outcome of gene–environment interaction is a notion widely accepted today; a clear understanding of how external factors are involved in disease pathogenesis is missing, however. In the case of AD, significant effort has been invested in the study of viral pathogens and their role in disease mechanisms. The current scoping review focuses on the purported role HHV-6 plays in AD pathogenesis. First, early studies demonstrating evidence of HHV-6 cantonment in either post-mortem AD brain specimens or in peripheral blood samples of living AD patients are reviewed. Next, selected examples of possible mechanisms whereby viral infection can directly or indirectly contribute to AD pathogenesis are presented, such as autophagy dysregulation, the interaction between miR155 and HHV-6, and amyloid-beta as an antimicrobial peptide. Finally, closely related topics such as HHV-6 penetration in the CNS, HHV-6 involvement in neuroinflammation, and a brief discussion on HHV-6 epigenetics are examined.

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  • Neurotropic pathogens such as human herpes virus, herpes simplex virus, hepatitis C virus, cytomegalovirus, varicella-zoster virus, and Epstein-Barr virus are associated with Alzheimer's disease neuropathology.

    “For example, neurotropic pathogens, such as human herpes virus (HHV), herpes simplex virus (HSV), hepatitis C virus (HCV), cytomegalovirus, varicella-zoster virus, and Epstein–Barr virus are associated with Alzheimer’s disease (AD) neuropathology [10,11,12,13].”

    From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [11]

    The Introduction (page unavailable) discusses HHV-6, HSV-1, CMV, and HCV in relation to Alzheimer’s disease mechanisms and reports higher viral quantities in some AD specimens than in controls. Section 4.3 also links viral infections to AD pathology, but the searched passages do not support the sentence’s inclusion of varicella-zoster or Epstein–Barr virus. (LLM, conf=0.86)

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Authors
Romanescu, C., Schreiner, T. G., & Mukovozov, I.
Affiliations
  • Clinical Section IV, “St. Parascheva” Infectious Disease Hospital, 700116 Iași, Romania
  • Carol Davila University of Medicine and Pharmacy (RO)
  • University of British Columbia (CA)
Corresponding author
  • Romanescu, Constantin
  • Schreiner, Thomas Gabriel
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2022-05-29
Volume
11
Issue
11
Pages
3061
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm11113061
PMC
PMC9181317
OpenAlex
W4281733165
Cited by
24
References
92
Citations by year
2026: 5 · 2025: 7 · 2024: 2 · 2023: 9 · 2022: 1
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • cIRcle (University of British Columbia) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Open Collections
Funders
authors
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Keywords
Alzheimer's disease, human herpesvirus 6, viral infection, pathogenesis, autophagy dysregulation, miR-155, amyloid-beta, antimicrobial peptides, neuroinflammation, epigenetics, blood-brain barrier penetration, gene-environment interaction

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