Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation





First Advisor

Dr. Donna M Wilcock


The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on Aging for evidence of HHV6 reactivation, both current and past, and how it relates to the rate of cognitive decline of these patients in eight cognitive domains. HHV6 reactivation was assessed by 1) patient self-report surveys, 2) anti-HHV6 serology, and 3) viral gene amplification via droplet digital PCR (ddCPR) in post-mortem temporal lobe and cerebellum tissue. We extracted RNA from these regions of postmortem tissue and performed the NanoString Human Inflammatory Panel to assess gene expression changes concomitant with HHV6 carriage and reactivation. Based on these results, we more closely examined changes to microglial activation and functional capacity based on the presence of HHV6. Finally, we investigated the role T-cells played in the development of these changes and subsequent pathology. Ultimately, we observed some predictive power from the patient reported survey in terms of cognitive decline. Serological evidence of reactivation showed no statistically significant relationship in any of the cognitive domains. ddPCR revealed no significant correlations related to HHV6 carriage. NanoString gene expression assays showed an upregulation of several neuroinflammatory genes, as well as microglial markers and T-cell signaling cytokines in cases with HHV6. We observed few differences in microglial activation, morphology, or phagocytosis as a function of HHV6. We did observe evidence of HHV6 within some amyloid beta plaques examined, and several T-cells surrounding plaques throughout diseased tissue with confirmed HHV6. These results contribute to the ongoing debate surrounding the role of HHV6 in the development of Alzheimer’s disease while providing evidence that suggests that reactivation may not be a key factor connecting HHV6 to Alzheimer’s disease.

Digital Object Identifier (DOI)