Since 1991, Ruth Itzhaki and her team at the University of Manchester Institute of Science and Technology in England have been systematically proving the connection between HSV1 and AD. Initially, her team was studying CNS viral infections in immunocompromised patients when an intuitive leap occurred. What if the viruses were already present in the brain, but in a latent phase (dormant)?
Itzhaki and her colleagues, Jamieson, Wilcock and others, proceeded to demonstrate that HSV1 is indeed present in the brains of the elderly, both those with AD and those who are healthy.7 HSV 1 DNA was most prevalent in the temporal and frontal lobes of the brain— the very parts affected by AD.8 But they did not find the viral DNA in the white blood cells of these individuals. The virus was only in the brain.9 In 1997, Itzhaki’s team showed that the likelihood of being positive for HSV1 DNA was much higher among patients who had the risk factor gene for AD — the APOE4 gene.10 They also established that having the APOE4 gene also made these patients four times more likely to have cold sores.
Itzhaki’s group then moved to tissue culture to study the effects of HSV1 on cultured neuronal cells. They found that HSV1 infection resulted in cultured immortalized neurons producing excess amyloid protein. They then demonstrated that mice infected with HSV1 developed an excessive accumulation of amyloid protein in their brains, mimicking AD.11
Further cell culture work revealed that HSV1 alters the processing of the precursor proteins leading to amyloid,12 resulting in abnormal accumulations of amyloid. Moreover, HSV1 increases the formation of a second abnormal protein, tau, which forms the neurofibrillary tangles commonly found in AD.13 Of great clinical interest, currently available antiviral medications, such as acyclovir, have been shown to slow, halt or reverse the accumulation of some of amyloid and tau proteins when applied to infected neurons in culture.14
Similarly, transgenic APOE4-positive mice infected with HSV1 developed amyloid accumulations and neurofibrillary tangles (resembling AD) at a much denser level than similar mice which were not exposed to the HSV1 virus.10 So, there is extensive evidence from pathological studies, cell culture studies, and animal studies, indicating that HSV1 has a role in causing or accelerating AD.
Recently, Itzhaki, Mee, and Wozniak found the most striking evidence to date. Using in situ hybridization of intact tissue samples, they have located DNA of HSV1 in slices of brain from people who had died of AD, as well as from elderly persons who had died of other causes. In the brains of patients with AD, the DNA of HSV1 was localized inside the amyloid plaques.15
In fact, 90% of the plaques examined contained HSV1 DNA and 72% of the viral DNA was localized to such plaques. In contrast, HSV1 DNA was more randomly distributed in elderly controls with only 24% of the DNA associated with plaques (which are much fewer in elderly controls).