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

Wilcock, Gordon K.; Combrinck, Marc; Wozniak, Matthew A.; Itzhaki, Ruth F.; Shipley, Suzanne J.


Gordon K. Wilcock

Marc Combrinck

Matthew A. Wozniak

Ruth F. Itzhaki

Suzanne J. Shipley


It was previously shown that herpes simplex virus type 1 (HSV1) DNA resides latently in a high proportion of aged brains and that in carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4), it confers a strong risk of Alzheimer's disease. It was suggested that initial entry of brain by HSV1 and any subsequent reactivation(s) would cause a type of limited encephalitis, the resulting damage being more harmful in APOE-ε4 carriers. Reactivation(s) would induce synthesis of intrathecal antibodies; these are long-lived after herpes simplex encephalitis so they were sought in cerebrospinal fluid (CSF) of Alzheimer's disease patients and age-matched normal subjects. Intrathecal antibodies to human herpes-virus 6 (HHV6) were also sought as DNA of this virus has been detected previously in a high proportion of Alzheimer's disease brains. Antibody indices for HSV and HHV6 were measured using indirect ELISA for IgG antibody, and single radial immunodiffusion was used for albumin, in serum and CSF. A raised antibody index (>1.5) indicative of virus-specific intrathecal HSV1 IgG synthesis was found in 14/27 (52%) Alzheimer's disease patients and 9/13 (69%) age-matched normals (difference non-significant). A raised antibody index to HHV6 was detected in 22% of the Alzheimer's disease patients and in no normals, so presumably this virus either did not reactivate in brain or it elicited only short-lived intrathecal antibodies. The HSV1 results confirm the original PCR findings that show the presence of HSV1 DNA sequences in many elderly brains, and indicate also that the whole functional HSV1 genome is present, and that the virus has replicated. © 2004 Wiley-Liss, Inc.


Wilcock, G. K., Combrinck, M., Wozniak, M. A., Itzhaki, R. F., & Shipley, S. J. (2005). Productive herpes simplex virus in brain of elderly normal subjects and Alzheimer's disease patients. Journal of Medical Virology, 75(2), 300-306.

Journal Article Type Article
Publication Date Feb 1, 2005
Journal Journal of Medical Virology
Print ISSN 0146-6615
Publisher Wiley
Peer Reviewed Not Peer Reviewed
Volume 75
Issue 2
Pages 300-306
Keywords herpes simplex virus type 1, human herpesvirus 6, intrathecal antibodies
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