Herpes Simplex Virus and Alzheimer’s Disease: The Present State of Clinical Evidence

Alzheimer´s disease (AD) and dementia have a probably multifactorial pathogenesis and, accordingly to several studies, human herpes simplex virus type 1 (HSV-1) infection may be related. The purpose of this review is to assess the updated clinical evidence towards the association between herpes infection and AD. We performed a PubMed/MEDLINE database research and included in this review randomized clinical trials on the subject of antivirals effectiveness and AD, and observational case-control studies and observational cohort studies regarding AD diagnosis (using clinical and/or histological methods) and HSV-1 detection (using molecular biology or immunohistochemical techniques). A total of 23 case-control and 3 cohort studies met the predetermined inclusion criteria. The results showed that AD was associated with HSV-1 in 22 of the 26 included studies, with most of them confirming that herpes infection is more prevalent in AD patients, when compared to control patients. A possible link between HSV-1 and AD was discussed and many different interpretations and hypothesis were considered. Evidence from observational studies suggests a possible relationship between the two conditions, but the role of HSV-1 infection in the pathogenesis of AD is not completely understood yet. Well-designed and large clinical trials are necessary to endorse this hypothesis and to consider the use of antiviral drugs as a potential alternative for prevention or reduction in the progression rate of AD in the future.