Herpes simplex virus and Alzheimer's disease

Ruth Itzhaki, MSc, PhD, MA, University of Manchester, Manchester, UK, discusses the relationship between viral infections and dementia, focusing on the herpes simplex virus type 1 (HSV-1). The Itzhaki lab was the first to detect HSV-1 in the brain of a high proportion of aged controls and Alzheimer's disease (AD) patients. The salient difference was that most AD patients carried an APOE-ε4 allele, a known susceptibility factor for AD, suggesting that HSV-1 in the brain and APOE-ε4 together were a major risk factor for AD. Several studies have been carried out using HSV-1-infected human-induced neural stem cells to examine the effects of HSV-1 infection on AD. HSV-1 infected cells showed AD-like features such as amyloid deposition. Additionally, treatment with antivirals reduced the magnitude of the changes, demonstrating the protective effects of antivirals. Over the last years, there has been an increase of publications supporting directly or indirectly the involvement of HSV-1 in AD. Evidence suggests that HSV-1 can enter the brain and reside in latent form. However, it can be reactivated by events such as stress, inflammation, or immunosuppression, causing a productive infection and consequent damage. Recurrent reactivation causes cumulative damage that could lead to AD. Further studies have also found that the varicella-zoster virus (VZV), like HSV-1, increases the risk of dementia. This interview was conducted during the 2022 World Congress on Controversies in Neurology (CONy) meeting.