The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Abstract

Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the pursuit of a better understanding of disease mechanisms; however, the ultimate goal of obtaining a viable treatment option remains elusive. Neurodegenerative disease as an outcome of gene–environment interaction is a notion widely accepted today; a clear understanding of how external factors are involved in disease pathogenesis is missing, however. In the case of AD, significant effort has been invested in the study of viral pathogens and their role in disease mechanisms. The current scoping review focuses on the purported role HHV-6 plays in AD patho-genesis. First, early studies demonstrating evidence of HHV-6 cantonment in either post-mortem AD brain specimens or in peripheral blood samples of living AD patients are reviewed. Next, selected examples of possible mechanisms whereby viral infection can directly or indirectly contribute to AD pathogenesis are presented, such as autophagy dysregulation, the interaction between miR155 and HHV-6, and amyloid-beta as an antimicrobial peptide. Finally, closely related topics such as HHV-6 penetration in the CNS, HHV-6 involvement in neuroinflammation, and a brief discussion on HHV-6 epigenetics are examined.