Herpes simplex virus type 1 (HSV1) is present in latent form in the brains of a high proportion of elderly people1 and is a risk factor for Alzheimer's disease in carriers of the type-4 allele of the apolipoprotein E gene (apoE-e4). ApoE-e4 is also a risk factor for cold sores.2,3 We have suggested that when HSV1 is reactivated in the nervous system the resulting damage is greater in apoE-e4 carriers than in people who carry the other apoE alleles. We recently detected antibodies to HSV1 in cerebrospinal fluid, substantiating our detection of HSV1 by polymerase chain reaction and showing that it does indeed reactivate (unpublished data). A clinical trial testing a synthetic amyloid peptide as immunotherapy for Alzheimer's disease was recently halted because 4 patients developed inflammation of the brain; in “some” of these 4 patients, a virus was detected in the cerebrospinal fluid.4
The results of René Verreault and colleagues5 raise the intriguing possibility that viruses other than HSV1 may directly influence Alzheimer's disease. Nonetheless, their findings could equally well be explained by an indirect effect: HSV1 reactivation can be triggered by inflammation, and vaccines would presumably prevent inflammation by preventing infection with the target virus, thus indirectly preventing HSV1 reactivation. Their study also supports the possibility that vaccination against HSV1 itself might prevent Alzheimer's disease; such vaccination is feasible now that the age at which primary infection occurs is rising. In fact, we have shown that vaccination of HSV1-infected mice with mixed HSV1 glycoproteins prevents establishment of latency in the brain.6
Finally, it would be interesting to know if the trend detected by Verreault and colleagues is dependent on the apoE-genotype. Such dependence has also been found for patients with herpes simplex encephalitis7 and for subjects infected with HIV but who have not yet developed AIDS.8
Ruth F. Itzhaki Curtis B. Dobson Molecular Neurobiology Laboratory Department of Optometry and Neuroscience University of Manchester Institute of Science and Technology Manchester, UK
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