Herpes simplex virus type 1 (HSV1) has been implicated in Alzheimers disease (AD) because of its ubiquity, its propensity for neuronal latency and because in herpes simplex encephalitis (HSE), it affects the same brain regions as those mainly damaged in AD. We established, using PCR, that HSV1 DNA is present in brain of most elderly people, including AD patients. Subsequently we found that in carriers of the type 4 allele of the gene for apolipoprotein E (APOE), the virus is a major risk factor for AD [1,2]. Strong supporting evidence (even if indirect) comes from our discovery that in five disorders of known viral origin, APOE determines the outcome of infection. These are: cold sores [1,2] and HSE , caused by HSV1; liver damage caused by hepatitis C virus ; and (in a study by Corder et al. 1998) dementia and peripheral neuropathy caused by HIV (pre-AIDS). Also, we have confirmed our PCR detection of the virus in elderly brains in finding that an appreciable proportion of elderly people have antibodies to HSV1 in their cerebrospinal fluid (these are known to be very long-lived after HSE) (submitted). These intrathecal antibodies are absent, as is HSV1 DNA, in the CNS of younger people. As for other herpesviruses, we have detected (by PCR) human herpesvirus 6 and cytomegalovirus DNA in brain of a high proportion respectively of AD patients  and those with vascular dementia ; whether the presence of these viruses confers a risk of the disease (as with HSV1) or is a consequence is uncertain. Supporting evidence for a viral role in dementia comes from studies by other groups showing an association of peripheral infection and its aftermath with decline in cognitive function in elderly cardiovascular patients and AD patients.
We are now investigating possible mechanisms of interaction of HSV1 and apoE, and the effect of HSV1 on the breakdown of amyloid precursor protein in cultured neuronal cells; compared to appropriate control cells, infected cells have increased amounts of a 55kDa C-terminal fragment of APP, although that of APP itself decreases, as expected.
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