Herpes simplex virus type 1, apolipoprotein E and Alzheimer' disease

Various infectious agents, and viruses in particular, have been proposed as potential causes of Alzheimer's disease. Herpes simplex virus type 1 (HSV-1) is one of the stronger candidates because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The body of evidence for the role of HSV-1 in Alzheimer's disease is contentious but centres around its presence in the regions of the brain affected by Alzheimer's disease. The fact that HSV-1 is also present in elderly patients without the disease suggests that the virus is not an independent cause of the condition. The incidence of Alzheimer's disease is highest in carriers of the apolipoprotein (APO) E-e4 allele who harbour HSV-1 DNA in the CNS, so it is possible that these agents are co-factors for the disease. However, studies investigating this have been small and limited by the need to access brain tissue from non-diseased APOE-e4 carriers. Human herpesvirus type 6 (HHV-6) is another virus investigated as a potential contributor to Alzheimer's disease. However, it is uncertain whether its presence is a cause or a consequence of the disease and it may be that HHV-6 merely exacerbates the potentially harmful effects of HSV-1 in APOE-e4 carriers. It is difficult to ascertain the role of an infectious agent in Alzheimer's disease due to the difficulty of establishing the timepoint at which the agent becomes involved. Further research into the possible link between herpesviruses and Alzheimer's disease is therefore required.