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Basic Science and Pathogenesis.

Axel Legrand1,2, Benoit Delatour1,3, Morgane Linard4,5

  • 1Paris Brain Institute (ICM), Inserm, CNRS, Sorbonne University, Paris, Ile de France, France.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Alphaherpesvirus infections, particularly Herpes Simplex Virus Type 1 (HSV-1), may contribute to Alzheimer's disease (AD) development by triggering neuroinflammation and protein aggregation. Studies show increased viral antibodies in AD patients, suggesting a link between infection and AD neuropathology.

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Area of Science:

  • Neurovirology
  • Neuroimmunology
  • Alzheimer's Disease Research

Background:

  • Alphaherpesviruses, including HSV-1 and VZV, are common human neurotropic viruses.
  • Previous research suggests a link between neurotropic herpesviruses and Alzheimer's disease (AD).
  • This study hypothesizes that HSV-1 neuro-invasion may initiate or exacerbate early AD lesions.

Purpose of the Study:

  • To investigate the neuropathological effects of HSV-1 infection.
  • To explore the association between alphaherpesvirus infection and Alzheimer's disease biomarkers.
  • To determine if HSV-1 infection contributes to AD pathogenesis.

Main Methods:

  • Utilized two animal models (cotton-rat and mouse) for HSV-1 infection studies.
  • Conducted histological and biochemical analyses to detect viral presence, neuroinflammation, and AD biomarkers (Aß, pTau).
  • Analyzed the Shatau human cohort for serological data, Locus Coeruleus integrity, neuroimaging markers, and CSF biomarkers.

Main Results:

  • HSV-1 neuro-invasion was confirmed in animal models, showing viral presence, neuroinflammation, and Aß/pTau deposition.
  • The Shatau cohort analysis revealed elevated anti-viral antibody titers in AD patients compared to controls.
  • Varicella-Zoster Virus (VZV) titers correlated with reduced Locus Coeruleus integrity and increased CSF AD biomarkers, while HSV-1 correlations were weaker.

Conclusions:

  • Findings support the hypothesis linking alphaherpesvirus infection and neuro-invasion to AD neuropathology.
  • The study suggests a potential causal role for viral infections in the development of Alzheimer's disease.
  • Further research is warranted to elucidate the precise mechanisms of viral contribution to AD.