Skip to main content
SpringerLink
Log in

HSV1 in Alzheimer’s disease: Myth or reality?

  • Review article
  • Published:
Translational Neuroscience

Abstract

Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly, characterized by the presence of cerebral amyloid plaques and neurofibrillary tangles. The causes of the disease are not well understood, especially considering that more than 95% of AD patients are non-familial. Due to the similarity of brain regions affected in herpes simplex encephalitis to those mainly affected in AD, and owing to the very high prevalence of latent herpes simplex virus type 1 (HSV1) infection, reactivation of HSV1 was proposed as one of the possible causes of AD. The trigeminal ganglion, located only a few millimeters from the entorhinal cortex, is the primary site of HSV1 latency, although other sites including the sensory neurons, the nodose ganglion of the vagus nerve and other regions of the brain may be involved, possibly in relation to very early neurofibrillary AD changes in the dorsal raphe, locus coeruleus and other brainstem nuclei. Novel data obtained upon infection of cultured neuronal cells and mouse brain with HSV1 further show that HSV1 infection causes intracellular amyloid-beta protein accumulation, as well as abnormal phosphorylation of tau protein, the major component of tangles. Another interesting fact is the existence of a significant degree of homology between HSV1 components and AD susceptibility genes. In this review we summarize findings that reveal connections between the two conditions, as well as different suggestions for the mechanisms of HSV1-induced AD. As most of the available results support a connection of AD and HSV1 infection, antiviral therapy should be taken into consideration for AD treatment following early diagnosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferri C. P., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., et al., Global prevalence of dementia: a Delphi consensus study, Lancet, 2005, 366, 2112–2117

    Article  PubMed  Google Scholar 

  2. Brickell K. L., Steinbart E. J., Rumbaugh M., Payami H., Schellenberg G. D., Van Deerlin V., et al., Early-onset Alzheimer disease in families with late-onset Alzheimer disease: a potential important subtype of familial Alzheimer disease, Arch Neurol, 2006, 63, 1307–1311

    Article  PubMed  Google Scholar 

  3. Bird T. D., Genetic aspects of Alzheimer disease, Genet Med, 2008, 10, 231–239

    Article  PubMed  CAS  Google Scholar 

  4. Bekris L. M., Yu C. E., Bird T. D., Tsuang D. W., Genetics of Alzheimer disease, J Geriatr Psychiatry Neurol, 2010, 23, 213–227

    Article  PubMed  Google Scholar 

  5. Dubois B., Feldman H. H., Jacova C., Dekosky S. T., Barberger-Gateau P., Cummings J., et al., Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria, Lancet Neurol, 2007, 6, 734–746

    Article  PubMed  Google Scholar 

  6. Hort J., O’Brien J. T., Gainotti G., Pirttila T., Popescu B. O., Rektorova I., et al., EFNS guidelines for the diagnosis and management of Alzheimer’s disease, Eur J Neurol, 2010, 17, 1236–1248

    Article  PubMed  CAS  Google Scholar 

  7. Hardy J. A., Higgins G. A., Alzheimer’s disease: the amyloid cascade hypothesis, Science, 1992, 256, 184–185

    Article  PubMed  CAS  Google Scholar 

  8. Goate A., Chartier-Harlin M. C., Mullan M., Brown J., Crawford F., Fidani L., et al., Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease, Nature, 1991, 349, 704–706

    Article  PubMed  CAS  Google Scholar 

  9. Hutton M., Lendon C. L., Rizzu P., Baker M., Froelich S., Houlden H., et al., Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17, Nature, 1998, 393, 702–705

    Article  PubMed  CAS  Google Scholar 

  10. Spillantini M. G., Murrell J. R., Goedert M., Farlow M. R., Klug A., Ghetti B., Mutation in the tau gene in familial multiple system tauopathy with presenile dementia, Proc Natl Acad Sci U S A, 1998, 95, 7737–7741

    Article  PubMed  CAS  Google Scholar 

  11. Šimić G., Gnjidić M., Kostović I., Cytoskeletal changes as an alternative view on Alzheimer’s disease, Period Biol, 1998, 100, 165–173

    Google Scholar 

  12. Braak H., Braak E., Diagnostic criteria for neuropathologic assessment of Alzheimer’s disease, Neurobiol Aging, 1997, 18, S85–88

    Article  PubMed  CAS  Google Scholar 

  13. Braak H., Del Tredici K., The pathological process underlying Alzheimer’s disease in individuals under thirty, Acta Neuropathol, 2011, 121, 171–181

    Article  PubMed  Google Scholar 

  14. Duyckaerts C., Tau pathology in children and young adults: can you still be unconditionally baptist?, Acta Neuropathol, 2011, 121, 145–147

    Article  PubMed  Google Scholar 

  15. Mangialasche F., Solomon A., Winblad B., Mecocci P., Kivipelto M., Alzheimer’s disease: clinical trials and drug development, Lancet Neurol, 2010, 9, 702–716

    Article  PubMed  CAS  Google Scholar 

  16. Bierer P., Conference report: the International Conference on Continuous Renal Replacement Therapies: San Diego, California—November 8–10, 1995, Aust Crit Care, 1996, 9, 17–19

    Article  PubMed  CAS  Google Scholar 

  17. Braak H., Braak E., Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol, 1991, 82, 239–259

    Article  PubMed  CAS  Google Scholar 

  18. Grinberg L. T., Rub U., Ferretti R. E., Nitrini R., Farfel J. M., Polichiso L., et al., The dorsal raphe nucleus shows phospho-tau neurofibrillary changes before the transentorhinal region in Alzheimer’s disease. A precocious onset?, Neuropathol Appl Neurobiol, 2009, 35, 406–416

    Article  PubMed  CAS  Google Scholar 

  19. Šimić G., Stanić G., Mladinov M., Jovanov-Milošević N., Kostović I., Hof P. R., Does Alzheimer’s disease begin in the brainstem?, Neuropathol Appl Neurobiol, 2009, 35, 532–554

    Article  PubMed  Google Scholar 

  20. Kapogiannis D., Mattson M. P., Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer’s disease, Lancet Neurol, 2011, 10, 187–198

    Article  PubMed  CAS  Google Scholar 

  21. Akiyama H., Barger S., Barnum S., Bradt B., Bauer J., Cole G. M., et al., Inflammation and Alzheimer’s disease, Neurobiol Aging, 2000, 21, 383–421

    Article  PubMed  CAS  Google Scholar 

  22. Mamelak M., Alzheimer’s disease, oxidative stress and mmahydroxybutyrate, Neurobiol Aging, 2007, 28, 1340–1360

    Article  PubMed  CAS  Google Scholar 

  23. Chayavichitsilp P., Buckwalter J. V., Krakowski A. C., Friedlander S. F., Herpes simplex, Pediatr Rev, 2009, 30, 119–129

    Article  PubMed  Google Scholar 

  24. Itzhaki R. F., Wozniak M. A., Herpes simplex virus type 1 in Alzheimer’s disease: the enemy within, J Alzheimers Dis, 2008, 13, 393–405

    PubMed  CAS  Google Scholar 

  25. Wagner E. K., Devi-Rao G., Feldman L. T., Dobson A. T., Zhang Y. F., Flanagan W. M., et al., Physical characterization of the herpes simplex virus latency-associated transcript in neurons, J Virol, 1988, 62, 1194–1202

    PubMed  CAS  Google Scholar 

  26. Fraser N. W., Lawrence W. C., Wroblewska Z., Gilden D. H., Koprowski H., Herpes simplex type 1 DNA in human brain tissue, Proc Natl Acad Sci U S A, 1981, 78, 6461–6465

    Article  PubMed  CAS  Google Scholar 

  27. Miller C. S., Danaher R. J., Jacob R. J., Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence, Crit Rev Oral Biol Med, 1998, 9, 541–562

    Article  PubMed  CAS  Google Scholar 

  28. Gesser R. M., Valyi-Nagy T., Altschuler S. M., Fraser N. W., Oraloesophageal inoculation of mice with herpes simplex virus type 1 causes latent infection of the vagal sensory ganglia (nodose ganglia), J Gen Virol, 1994, 75( Pt 9), 2379–2386

    Article  PubMed  Google Scholar 

  29. Baringer J. R., Pisani P., Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction, Ann Neurol, 1994, 36, 823–829

    Article  PubMed  CAS  Google Scholar 

  30. Itzhaki R. F., Wozniak M. A., Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer’s disease and other disorders, Prog Lipid Res, 2006, 45, 73–90

    Article  PubMed  CAS  Google Scholar 

  31. Denaro F. J., Staub P., Colmer J., Freed D. M., Coexistence of Alzheimer disease neuropathology with herpes simplex encephalitis, Cell Mol Biol (Noisy-le-grand), 2003, 49, 1233–1240

    CAS  Google Scholar 

  32. WuDunn D., Spear P. G., Initial interaction of herpes simplex virus with cells is binding to heparan sulfate, J Virol, 1989, 63, 52–58

    PubMed  CAS  Google Scholar 

  33. Krummenacher C., Nicola A. V., Whitbeck J. C., Lou H., Hou W., Lambris J. D., et al., Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry, J Virol, 1998, 72, 7064–7074

    PubMed  CAS  Google Scholar 

  34. Bender F. C., Whitbeck J. C., Ponce de Leon M., Lou H., Eisenberg R. J., Cohen G. H., Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry, J Virol, 2003, 77, 9542–9552

    Article  PubMed  CAS  Google Scholar 

  35. Pandav R., Dodge H. H., DeKosky S. T., Ganguli M., Blood pressure and cognitive impairment in India and the United States: a crossnational epidemiological study, Arch Neurol, 2003, 60, 1123–1128

    Article  PubMed  Google Scholar 

  36. Mufson E. J., Ikonomovic M. D., Styren S. D., Counts S. E., Wuu J., Leurgans S., et al., Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease, Arch Neurol, 2003, 60, 1143–1148

    Article  PubMed  Google Scholar 

  37. Hardy J., Alzheimer’s disease: genetic evidence points to a single pathogenesis, Ann Neurol, 2003, 54, 143–144

    Article  PubMed  CAS  Google Scholar 

  38. Renvoize E. B., Awad I. O., Hambling M. H., A sero-epidemiological study of conventional infectious agents in Alzheimer’s disease, Age Ageing, 1987, 16, 311–314

    Article  PubMed  CAS  Google Scholar 

  39. Fukumoto H., Tennis M., Locascio J. J., Hyman B. T., Growdon J. H., Irizarry M. C., Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels, Arch Neurol, 2003, 60, 958–964

    Article  PubMed  Google Scholar 

  40. Saunders A. M., Schmader K., Breitner J. C., Benson M. D., Brown W. T., Goldfarb L., et al., Apolipoprotein E epsilon 4 allele distributions in late-onset Alzheimer’s disease and in other amyloid-forming diseases, Lancet, 1993, 342, 710–711

    Article  PubMed  CAS  Google Scholar 

  41. Nathan B. P., Chang K. C., Bellosta S., Brisch E., Ge N., Mahley R. W., et al., The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization, J Biol Chem, 1995, 270, 19791–19799

    Article  PubMed  CAS  Google Scholar 

  42. Poirier J., Minnich A., Davignon J., Apolipoprotein E, synaptic plasticity and Alzheimer’s disease, Ann Med, 1995, 27, 663–670

    Article  PubMed  CAS  Google Scholar 

  43. Arendt T., Schindler C., Bruckner M. K., Eschrich K., Bigl V., Zedlick D., et al., Plastic neuronal remodeling is impaired in patients with Alzheimer’s disease carrying apolipoprotein epsilon 4 allele, J Neurosci, 1997, 17, 516–529

    PubMed  CAS  Google Scholar 

  44. Corder E. H., Robertson K., Lannfelt L., Bogdanovic N., Eggertsen G., Wilkins J., et al., HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy, Nat Med, 1998, 4, 1182–1184

    Article  PubMed  CAS  Google Scholar 

  45. Isoniemi H., Tenovuo O., Portin R., Himanen L., Kairisto V., Outcome of traumatic brain injury after three decades—relationship to ApoE genotype, J Neurotrauma, 2006, 23, 1600–1608

    Article  PubMed  Google Scholar 

  46. Wozniak M. A., Itzhaki R. F., Faragher E. B., James M. W., Ryder S. D., Irving W. L., Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus, Hepatology, 2002, 36, 456–463

    Article  PubMed  CAS  Google Scholar 

  47. Itzhaki R. F., Lin W. R., Shang D., Wilcock G. K., Faragher B., Jamieson G. A., Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease, Lancet, 1997, 349, 241–244

    Article  PubMed  CAS  Google Scholar 

  48. Lin W. R., Wozniak M. A., Esiri M. M., Klenerman P., Itzhaki R. F., Herpes simplex encephalitis: involvement of apolipoprotein E genotype, J Neurol Neurosurg Psychiatry, 2001, 70, 117–119

    Article  PubMed  CAS  Google Scholar 

  49. Burgos J. S., Ramirez C., Sastre I., Valdivieso F., Effect of apolipoprotein E on the cerebral load of latent herpes simplex virus type 1 DNA, J Virol, 2006, 80, 5383–5387

    Article  PubMed  CAS  Google Scholar 

  50. Burgos J. S., Ramirez C., Guzman-Sanchez F., Alfaro J. M., Sastre I., Valdivieso F., Hematogenous vertical transmission of herpes simplex virus type 1 in mice, J Virol, 2006, 80, 2823–2831

    Article  PubMed  CAS  Google Scholar 

  51. Burgos J. S., Ramirez C., Sastre I., Valdivieso F., Apolipoprotein E genotype influences vertical transmission of herpes simplex virus type 1 in a gender specific manner, Aging Cell, 2007, 6, 841–842

    Article  PubMed  CAS  Google Scholar 

  52. Miller R. M., Federoff H. J., Isoform-specific effects of ApoE on HSV immediate early gene expression and establishment of latency, Neurobiol Aging, 2008, 29, 71–77

    Article  PubMed  CAS  Google Scholar 

  53. Itzhaki R. F., Lin W. R., Herpes simplex virus type I in brain and the type 4 allele of the apolipoprotein E gene are a combined risk factor for Alzheimer’s disease, Biochem Soc Trans, 1998, 26, 273–277

    PubMed  CAS  Google Scholar 

  54. Bullido M. J., Martinez-Garcia A., Artiga M. J., Aldudo J., Sastre I., Gil P., et al., A TAP2 genotype associated with Alzheimer’s disease in APOE4 carriers, Neurobiol Aging, 2007, 28, 519–523

    Article  PubMed  CAS  Google Scholar 

  55. Itzhaki R. F., Wozniak M. A., Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer’s disease and other disorders, Prog Lipid Res, 2006, 45, 73–90

    Article  PubMed  CAS  Google Scholar 

  56. Hill J. M., Steiner I., Matthews K. E., Trahan S. G., Foster T. P., Ball M. J., Statins lower the risk of developing Alzheimer’s disease by limiting lipid raft endocytosis and decreasing the neuronal spread of Herpes simplex virus type 1, Med Hypotheses, 2005, 64, 53–58

    Article  PubMed  CAS  Google Scholar 

  57. Wolozin B., Kellman W., Ruosseau P., Celesia G. G., Siegel G., Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors, Arch Neurol, 2000, 57, 1439–1443

    Article  PubMed  CAS  Google Scholar 

  58. Jamieson G. A., Maitland N. J., Wilcock G. K., Yates C. M., Itzhaki R. F., Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type, J Pathol, 1992, 167, 365–368

    Article  PubMed  CAS  Google Scholar 

  59. Wozniak M. A., Shipley S. J., Combrinck M., Wilcock G. K., Itzhaki R. F., Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer’s disease patients, J Med Virol, 2005, 75, 300–306

    Article  PubMed  Google Scholar 

  60. Jamieson G. A., Maitland N. J., Wilcock G. K., Craske J., Itzhaki R. F., Latent herpes simplex virus type 1 in normal and Alzheimer’s disease brains, J Med Virol, 1991, 33, 224–227

    Article  PubMed  CAS  Google Scholar 

  61. Cheon M. S., Bajo M., Gulesserian T., Cairns N., Lubec G., Evidence for the relation of herpes simplex virus type 1 to Down syndrome and Alzheimer’s disease, Electrophoresis, 2001, 22, 445–448

    Article  PubMed  CAS  Google Scholar 

  62. Kamal A., Stokin G. B., Yang Z., Xia C. H., Goldstein L. S., Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I, Neuron, 2000, 28, 449–459

    Article  PubMed  CAS  Google Scholar 

  63. Satpute-Krishnan P., DeGiorgis J. A., Bearer E. L., Fast anterograde transport of herpes simplex virus: role for the amyloid precursor protein of alzheimer’s disease, Aging Cell, 2003, 2, 305–318

    Article  PubMed  CAS  Google Scholar 

  64. Shipley S. J., Parkin E. T., Itzhaki R. F., Dobson C. B., Herpes simplex virus interferes with amyloid precursor protein processing, BMC Microbiol, 2005, 5, 48

    Article  PubMed  Google Scholar 

  65. Wozniak M. A., Itzhaki R. F., Shipley S. J., Dobson C. B. Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett, 2007, 429, 95–100

    Article  PubMed  CAS  Google Scholar 

  66. Piacentini R., Civitelli L., Ripoli C., Marcocci M. E., De Chiara G., Garaci E., et al., HSV-1 promotes Ca(2+)-mediated APP phosphorylation and Abeta accumulation in rat cortical neurons, Neurobiol Aging, 2010, DOI: 10.1016/j.biolaging.2010.06.009

  67. Wozniak M. A., Mee A. P., Itzhaki R. F., Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques, J Pathol, 2009, 217, 131–138

    Article  PubMed  CAS  Google Scholar 

  68. Kammerman E. M., Neumann D. M., Ball M. J., Lukiw W., Hill J. M., Senile plaques in Alzheimer’s diseased brains: possible association of beta-amyloid with herpes simplex virus type 1 (HSV-1) L-particles, Med Hypotheses, 2006, 66, 294–299

    Article  PubMed  CAS  Google Scholar 

  69. Lukiw W. J., Cui J. G., Yuan L. Y., Bhattacharjee P. S., Corkern M., Clement C., et al., Acyclovir or Abeta42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells, Neuroreport, 2010, 21, 922–927

    Article  PubMed  CAS  Google Scholar 

  70. Wozniak M. A., Frost A. L., Itzhaki R. F., Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1, J Alzheimers Dis, 2009, 16, 341–350

    PubMed  CAS  Google Scholar 

  71. Ziaie Z., Brinker J. M., Kefalides N. A., Lithium chloride suppresses the synthesis of messenger RNA for infected cell protein-4 and viral deoxyribonucleic acid polymerase in herpes simplex virus-1 infected endothelial cells, Lab Invest, 1994, 70, 29–38

    PubMed  CAS  Google Scholar 

  72. Advani S. J., Weichselbaum R. R., Roizman B., The role of cdc2 in the expression of herpes simplex virus genes, Proc Natl Acad Sci U S A, 2000, 97, 10996–11001

    Article  PubMed  CAS  Google Scholar 

  73. Vincent I., Jicha G., Rosado M., Dickson D. W., Aberrant expression of mitotic cdc2/cyclin B1 kinase in degenerating neurons of Alzheimer’s disease brain, J Neurosci, 1997, 17, 3588–3598

    PubMed  CAS  Google Scholar 

  74. Letenneur L., Peres K., Fleury H., Garrigue I., Barberger-Gateau P., Helmer C., et al., Seropositivity to herpes simplex virus antibodies and risk of Alzheimer’s disease: a population-based cohort study, PLoS One, 2008, 3, e3637

    Article  PubMed  Google Scholar 

  75. Bullido M. J., Martinez-Garcia A., Tenorio R., Sastre I., Munoz D. G., Frank A., et al., Double stranded RNA activated EIF2 alpha kinase (EIF2AK2; PKR) is associated with Alzheimer’s disease, Neurobiol Aging, 2008, 29, 1160–1166

    Article  PubMed  CAS  Google Scholar 

  76. Hill J. M., Zhao Y., Clement C., Neumann D. M., Lukiw W. J., HSV-1 infection of human brain cells induces miRNA-146a and Alzheimertype inflammatory signaling, Neuroreport, 2009, 20, 1500–1505

    Article  PubMed  CAS  Google Scholar 

  77. Carter C. J., Alzheimer’s disease: a pathogenetic autoimmune disorder caused by herpes simplex in a gene-dependent manner, Int J Alzheimers Dis, 2010, 2010, 140539

    PubMed  CAS  Google Scholar 

  78. Santana S., Recuero M., Bullido M. J., Valdivieso F., Aldudo J., Herpes simplex virus type I induces the accumulation of intracellular betaamyloid in autophagic compartments and the inhibition of the nonamyloidogenic pathway in human neuroblastoma cells, Neurobiol Aging, 2011

  79. Esiri M. M., Biddolph S. C., Morris C. S., Prevalence of Alzheimer plaques in AIDS, J Neurol Neurosurg Psychiatry, 1998, 65, 29–33

    Article  PubMed  CAS  Google Scholar 

  80. Dhingra V., Li Q., Allison A. B., Stallknecht D. E., Fu Z. F., Proteomic profiling and neurodegeneration in West-Nile-virus-infected neurons, J Biomed Biotechnol, 2005, 2005, 271–279

    Article  PubMed  CAS  Google Scholar 

  81. Little C. S., Hammond C. J., MacIntyre A., Balin B. J., Appelt D. M., Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice, Neurobiol Aging, 2004, 25, 419–429

    Article  PubMed  CAS  Google Scholar 

  82. Renvoize E. B., Awad I. O., Hambling M. H., A sero-epidemiological study of conventional infectious agents in Alzheimer’s disease, Age Ageing, 1987, 16, 311–314

    Article  PubMed  CAS  Google Scholar 

  83. Wozniak M. A., Shipley S. J., Combrinck M., Wilcock G. K., Itzhaki R. F., Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer’s disease patients, J Med Virol, 2005, 75, 300–306

    Article  PubMed  Google Scholar 

  84. Honjo K., van Reekum R., Verhoeff N. P., Alzheimer’s disease and infection: do infectious agents contribute to progression of Alzheimer’s disease?, Alzheimers Dement, 2009, 5, 348–360

    Article  PubMed  Google Scholar 

  85. Gerard H. C., Dreses-Werringloer U., Wildt K. S., Deka S., Oszust C., Balin B. J., et al., Chlamydophila (Chlamydia) pneumoniae in the Alzheimer’s brain, FEMS Immunol Med Microbiol, 2006, 48, 355–366

    Article  PubMed  CAS  Google Scholar 

  86. Balin B. J., Little C. S., Hammond C. J., Appelt D. M., Whittum-Hudson J. A., Gerard H. C., et al., Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease, J Alzheimers Dis, 2008, 13, 371–380

    PubMed  CAS  Google Scholar 

  87. Miklossy J., Chronic inflammation and amyloidogenesis in Alzheimer’s disease — role of Spirochetes, J Alzheimers Dis, 2008, 13, 381–391

    PubMed  CAS  Google Scholar 

  88. Itzhaki R. F., Wozniak M. A., Alzheimer’s disease and infection: Do infectious agents contribute to progression of Alzheimer’s disease?, Alzheimers Dement, 2010, 6, 83–84; author reply 5

    Article  PubMed  Google Scholar 

  89. Wozniak M. A., Itzhaki R. F., Antiviral agents in Alzheimer’s disease: hope for the future?, Ther Adv Neurol Disord, 2010, 3, 141–152

    Article  PubMed  CAS  Google Scholar 

  90. Lin W. R., Jennings R., Smith T. L., Wozniak M. A., Itzhaki R. F., Vaccination prevents latent HSV1 infection of mouse brain, Neurobiol Aging, 2001, 22, 699–703

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia

    Tea Špeljko, David Jutric & Goran Šimić

Authors
  1. Tea Špeljko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Jutric
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Goran Šimić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Goran Šimić.

About this article

Cite this article

Špeljko, T., Jutric, D. & Šimić, G. HSV1 in Alzheimer’s disease: Myth or reality?. Translat.Neurosci. 2, 61–68 (2011). https://doi.org/10.2478/s13380-011-0009-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s13380-011-0009-2

Keywords

Search

Navigation