Abstract
BACKGROUND: In studies on the possible role of viruses in the aetiopathogenesis of Alzheimer's disease, herpes simplex virus type 1 (HSV1) DNA was detected by the polymerase chain reaction (PCR) in a high proportion of normal elderly people and of patients with Alzheimer's disease. The combination of HSV1 and a host factor, the type 4 allele of the gene for apolipoprotein E, is a strong risk factor for the disease. METHODS: Brain specimens were examined for another herpes virus, varicella zoster (VZV), which, like HSV1, is neurotropic, has a predilection for residing latently in the peripheral nervous system, and can reactivate. RESULTS: Using primers for sequences in the VZV origin of replication gene or thymidine kinase gene, VZV DNA was not found in any of 24 samples (18 HSV1 positive), from 17 patients with Alzheimer's disease, nor in 20 samples (12 HSV1 positive from 12 aged normal people. Hybridisation of the PCR products with a radiolabelled oligonucleotide probe capable of detecting less than 10 copies of the target sequence, confirmed the absence of VZV DNA. CONCLUSION: The presence of one neurotropic virus--HSV1--and the absence of another--VZV--in aged human brains is consistent with a role for HSV1 in the aetiology of Alzheimer's disease.
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- Alexander R. C., Cabirac G., Lowenkopf T., Casanova M., Kleinman J., Wyatt R. J., Kirch D. G. Search for evidence of herpes simplex virus, type 1, or varicella-zoster virus infection in postmortem brain tissue from schizophrenic patients. Acta Psychiatr Scand. 1992 Nov;86(5):418–420. doi: 10.1111/j.1600-0447.1992.tb03290.x. [DOI] [PubMed] [Google Scholar]
- Corder E. H., Saunders A. M., Strittmatter W. J., Schmechel D. E., Gaskell P. C., Small G. W., Roses A. D., Haines J. L., Pericak-Vance M. A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993 Aug 13;261(5123):921–923. doi: 10.1126/science.8346443. [DOI] [PubMed] [Google Scholar]
- Doty R. L., Reyes P. F., Gregor T. Presence of both odor identification and detection deficits in Alzheimer's disease. Brain Res Bull. 1987 May;18(5):597–600. doi: 10.1016/0361-9230(87)90129-8. [DOI] [PubMed] [Google Scholar]
- 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 Jan 25;349(9047):241–244. doi: 10.1016/S0140-6736(96)10149-5. [DOI] [PubMed] [Google Scholar]
- Itzhaki R. F. Possible factors in the etiology of Alzheimer's disease. Mol Neurobiol. 1994 Aug-Dec;9(1-3):1–13. doi: 10.1007/BF02816099. [DOI] [PubMed] [Google Scholar]
- 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 Aug;167(4):365–368. doi: 10.1002/path.1711670403. [DOI] [PubMed] [Google Scholar]
- Kellogg D. E., Sninsky J. J., Kwok S. Quantitation of HIV-1 proviral DNA relative to cellular DNA by the polymerase chain reaction. Anal Biochem. 1990 Sep;189(2):202–208. doi: 10.1016/0003-2697(90)90108-l. [DOI] [PubMed] [Google Scholar]
- Klapper P. E., Cleator G. M., Longson M. Mild forms of herpes encephalitis. J Neurol Neurosurg Psychiatry. 1984 Nov;47(11):1247–1250. doi: 10.1136/jnnp.47.11.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liedtke W., Opalka B., Zimmermann C. W., Lignitz E. Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J Neurol Sci. 1993 May;116(1):6–11. doi: 10.1016/0022-510x(93)90082-a. [DOI] [PubMed] [Google Scholar]
- Lin W. R., Shang D., Itzhaki R. F. Neurotropic viruses and Alzheimer disease. Interaction of herpes simplex type 1 virus and apolipoprotein E in the etiology of the disease. Mol Chem Neuropathol. 1996 May-Aug;28(1-3):135–141. doi: 10.1007/BF02815215. [DOI] [PubMed] [Google Scholar]
- Lin W. R., Shang D., Wilcock G. K., Itzhaki R. F. Alzheimer's disease, herpes simplex virus type 1, cold sores and apolipoprotein E4. Biochem Soc Trans. 1995 Nov;23(4):594S–594S. doi: 10.1042/bst023594s. [DOI] [PubMed] [Google Scholar]
- Mahalingam R., Wellish M., Wolf W., Dueland A. N., Cohrs R., Vafai A., Gilden D. Latent varicella-zoster viral DNA in human trigeminal and thoracic ganglia. N Engl J Med. 1990 Sep 6;323(10):627–631. doi: 10.1056/NEJM199009063231002. [DOI] [PubMed] [Google Scholar]
- Meier J. L., Straus S. E. Comparative biology of latent varicella-zoster virus and herpes simplex virus infections. J Infect Dis. 1992 Aug;166 (Suppl 1):S13–S23. doi: 10.1093/infdis/166.supplement_1.s13. [DOI] [PubMed] [Google Scholar]
- Nahmias A. J., Whitley R. J., Visintine A. N., Takei Y., Alford C. A., Jr Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis. 1982 Jun;145(6):829–836. doi: 10.1093/infdis/145.6.829. [DOI] [PubMed] [Google Scholar]
- Oxman M. N. Immunization to reduce the frequency and severity of herpes zoster and its complications. Neurology. 1995 Dec;45(12 Suppl 8):S41–S46. doi: 10.1212/wnl.45.12_suppl_8.s41. [DOI] [PubMed] [Google Scholar]
- Whitley R., Lakeman A. D., Nahmias A., Roizman B. Dna restriction-enzyme analysis of herpes simplex virus isolates obtained from patients with encephalitis. N Engl J Med. 1982 Oct 21;307(17):1060–1062. doi: 10.1056/NEJM198210213071706. [DOI] [PubMed] [Google Scholar]