Alzheimer's disease plaques and tangles: Cemeteries of a Pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction

@article{Carter2011AlzheimersDP,
  title={Alzheimer's disease plaques and tangles: Cemeteries of a Pyrrhic victory of the immune defence network against herpes simplex infection at the expense of complement and inflammation-mediated neuronal destruction},
  author={Chris J. Carter},
  journal={Neurochemistry International},
  year={2011},
  volume={58},
  pages={301-320}
}
  • C. Carter
  • Published 1 February 2011
  • Biology
  • Neurochemistry International

Herpesviral infections and antimicrobial protection for Alzheimer's disease: Implications for prevention and treatment

Support for a hypothesis of herpesviral infections and antimicrobial protection in the development of AD is summarized, and the implications for future prevention and treatment of the disease are discussed.

Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

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  • C. Carter
  • Biology
    International journal of Alzheimer's disease
  • 2011
Alzheimer's disease susceptibility genes, APP and gamma-secretase, are involved in the herpes simplex life cycle, and that of other suspect pathogens, and may thus be causative agents, whose effects are conditioned by genes.

Viral Hypothesis and Antiviral Treatment in Alzheimer’s Disease

  • D. Devanand
  • Biology, Medicine
    Current Neurology and Neuroscience Reports
  • 2018
An antiviral treatment trial in AD is clearly warranted and a phase II treatment trial with valacyclovir, an anti-HSV drug, recently began with evaluation of clinical and biomarker outcomes.

Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.

  • C. Carter
  • Psychology, Biology
    Pathogens and disease
  • 2013
Overlapping susceptibility gene/interactome data sets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies.

Infectious Agents and Neurodegeneration

This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.

PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System

NGF or tau antibodies promote beta-amyloid deposition, neurofibrillary tangles, or cholinergic neuronal loss, and are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes.

Antiviral therapy: Valacyclovir Treatment of Alzheimer’s Disease (VALAD) Trial: protocol for a randomised, double-blind, placebo-controlled, treatment trial

Patients on valacyclovir are hypothesised to show smaller cognitive and functional decline, and, using 18F-Florbetapir positron emission tomography (PET), to show less amyloid and tau accumulation, respectively, in a randomised, double-blind, 78-week phase II proof-of-concept trial.

Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer’s disease

The findings support an association between HSV infection and AD and a potential interaction betweenHSV status and APOE4 and reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.

References

SHOWING 1-10 OF 182 REFERENCES

Alzheimer's disease-specific tau phosphorylation is induced by herpes simplex virus type 1.

The 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, and point to the use of antiviral agents to slow the progression of the Disease.

Stimulation of Enveloped Virus Infection by β-Amyloid Fibrils*

It is reported that Aβ fibrils stimulated, by 5–20-fold, infection of target cells expressing CD4 and an appropriate coreceptor by multiple HIV-1 isolates but did not permit infection of cells lacking these receptors, and that amyloidogenic peptides could be useful in enhancing gene transfer by enveloped viral vectors.

Herpes simplex virus type 1 and Alzheimer’s disease: The autophagy connection

HSV1 generates the main components of amyloid plaques and neurofibrillary tangles—β-amyloid (Aβ) and abnormally phosphorylated tau but also prevents degradation of these aberrant proteins, leading to their accumulation and deposition, and eventually to AD.

Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques

The present data suggest that this virus is a major cause of amyloid plaques and hence probably a significant aetiological factor in Alzheimer's disease, and point to the usage of antiviral agents to treat the disease and possibly of vaccination to prevent it.

Neuronal cytoskeletal dynamic modification and neurodegeneration induced by infection with herpes simplex virus type 1.

It is shown that infection of mice neuronal cultures with HSV-1 result in marked neurite damage and neuronal death, and this in vitro model of infection suggests a possible link between HSv-1 infection and neuronal cytoskeletal disruption.

High susceptibility of a human oligodendroglial cell line to herpes simplex type 1 infection

It is concluded that human oligodendrocyte-like cells are highly susceptible to HSV-1 infection, and the implications for central nervous system viral infection are discussed.

Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer's disease patients

The HSV 1 results confirm the original PCR findings that show the presence of HSV1 DNA sequences in many elderly brains, and indicate also that the whole functionalHSV1 genome is present, and that the virus has replicated.
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