In the wake of several recent failures of Alzheimer’s therapies targeting beta-amyloid (a protein that makes up amyloid plaques in Alzheimer’s) there is a growing interest in novel ideas on what may cause or accelerate the progression of Alzheimer’s disease. Since the 1980s, growing evidence has suggested that infection with herpes simplex virus (HSV)-1 may play a role.
HSV-1 is a member of the herpesvirus family, which includes HSV-1 and HSV-2 (which cause cold sores and genital herpes, respectively), varicella zoster virus (which causes chickenpox), cytomegalovirus, and Epstein-Barr virus. Although herpesvirus is very common in the general population, many who are infected never develop symptoms. After infection, HSV-1 can evade the immune system and remain latent by hiding in the nervous system. However, in certain conditions, such as stress or when the immune system is suppressed, HSV-1 can reactivate – that is replicate, spread, and possibly cause another cold sore. In fact, a high proportion of cognitively healthy elderly individuals and Alzheimer’s patients have HSV-1 viral DNA in brain tissue after death .
The 11th International Conference on HHV-6 and HHV-7 last month brought together researchers studying human herpesvirus with researchers studying Alzheimer’s disease to discuss a possible link between the two. The consensus of the meeting was that herpesviruses do not cause Alzheimer’s disease but may accelerate its progression. However, more work is needed to uncover this connection. Here we review some of the evidence.
How might an HSV infection increase the risk of Alzheimer’s disease? One possibility is that reactivation of HSV-1 in elderly individuals who are stressed or have suppressed immune system may damage the brain by increasing inflammation [6; 7]. Another interesting possibility is the potential role of beta-amyloid having anti-microbial properties. It is thought that beta-amyloid may protect the brain by binding to and killing infectious microbes. Indeed, a recent laboratory study suggested that infection with HSV-1 may accelerate amyloid deposition, and that beta-amyloid may offer protection from developing herpes simplex encephalitis, a rare HSV-1 brain infection .
Many questions remain regarding the connection between HSV-1 and Alzheimer’s disease. One ongoing clinical trial from New York State Psychiatric Institute is recruiting 130 individuals with mild Alzheimer’s disease who also have HSV-1 or HSV-2 in their blood. Patients will receive an anti-viral drug, valacyclovir, or a placebo for 78 weeks to see if there are any benefits in cognition or beta-amyloid accumulation. Other infectious pathogens, including cytomegalovirus, Chlamydophila pneumoniae, and periodontal pathogens, have been linked to Alzheimer’s disease . The NIH recently decided that a better understanding of the relationship between microbial pathogens and Alzheimer’s disease is a high priority topic and announced it would fund more research in this area. With more research, we will better understand whether HSV-1 infection may accelerate Alzheimer’s disease, how to identify patients in whom HSV-1 may be a contributing factor to the disease, and whether taking an antiviral medication may slow its progression.
Nick McKeehan is Assistant Director, Aging and Alzheimer's Prevention at the Alzheimer’s Drug Discovery Foundation. He served as Chief Intern at Mid Atlantic Bio Angels (MABA) and was a research technician at Albert Einstein College of Medicine investigating repair capabilities of the brain. He received a bachelor of science degree in biology from Purdue University, where he was awarded a Howard Hughes Scholarship. Mr. McKeehan also writes about the biotechnology industry for 1st Pitch Life Science.
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