Does Herpes Cause Alzheimer’s Disease?
Tags: Alzheimers, Virus, Health, Cogs163, Herpes

Linda Reyna

When the word “herpes” comes to mind, most of us tend to associate it with sexually transmitted genital ulcers. This schema is known as Type 2 herpes. It’s estimated that 67% of the population has been infected with another form of the herpes virus, type 1 (HSV1). Most people are either infected during infancy or old age due to the body’s week immunity. This viral infection causes cold sores around the mouth in about 20–40% of people while the rest don’t show any symptoms, not realizing they may be infected. The concerning part is that once your body is infected it retains the virus for life. The bizarre hypothesis that herpes is linked to Alzheimer’s Disease was proposed many decades ago. As it was being legitimized, it was confirmed that HSV1 alone is not a factor for developing Alzheimer’s Disease but rather for the 10–15% of the population who also carry a specific gene, APOE-4. This combination of the virus and a variant form of the gene,(E4),increases your risk by 1,100%! This evidence might suggest more of a potential effectiveness for antivirals as an AD treatment or even as a vaccine rather than a direct causal factor for AD.

What is HSV1?

Once infected with HSV1, the virus lingers in the body either actively or passively. It periodically reactives under episodes of stress, immunosuppression or inflammation. The virus is linked to AD because it causes additional similar pathologies seen in AD through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis, which are all known to lead to AD. The virus has the ability to cause accumulation of a protein called beta amyloid (Aβ), the hallmark characteristic for AD. There is a misconception that beta amyloid is bad but its basically our brain’s sweat from working hard all day. It’s just a by-product of the brain’s constant activity. But like anything in the world, too much of it is harmful. It’s actually been found that Aβ is an immune protein that protects against fungal and bacterial infections: its produced as an AMP in response to HSV and other brain infections which leads to Aβ plaques. It was also shown that the combination of Aβ and HSV signaled the production of inflammation. This self perpetuating cycle of chronic inflammation is known to be another significant factor in AD development.

What is APOE?

Apolipoprotein-E is a protein involved in the transport of lipids that is strongly linked to the development of AD. The type 4 allele (E4) is present in approximately 10–15% of people. Polymorphisms in this gene affects brain susceptibility to the HSV-1 infection. Having one copy of E4 can increase your risk of AD by 200% while E2 actually reduces the risk by 40%! E4 seems to facilitate HSV1 latency in the brain much more than the other alleles. It is considered to assist in the reactivation, or “turn on” the virus that leads to other metabolic and immune responses that are strongly associated with Alzheimer’s. The collection of data shows the direct relationship between HSV1 and APOE4 but the mechanisms by which they interact are still very unclear. Understanding this would be the crucial stepping stone to discovering how to manipulate this interaction to possibly prevent or even cure the disease.

As of today we know HSV1 has a strong harmful effect on cognition. However, we can not go as far as saying herpes virus alone is the cause of Alzheimer’s Disease. It is the unsolved interaction between the activated virus and a specific variant of a gene in the brain that allows for a cascade to unfold into the development of the disease. The only way to prove causation would be to effectively prevent the disease by vaccination against the virus, or to reduce the progression with antiviral treatment.

References:

Burgos, Javier S., et al. “Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA.” Journal of Virology, American Society for Microbiology Journals, 1 June 2006, jvi.asm.org/content/80/11/5383.

Itzhaki, Ruth. “Alzheimer’s Disease: Mounting Evidence That Herpes Virus Is a Cause.” The Conversation, The Conversation, 17 Dec. 2018, theconversation.com/alzheimers-disease-mounting-evidence-that-herpes-virus-is-a-cause-104943

Itzhaki, Ruth. “ApoE-viral interactions.” Nature Medicine, 1 Dec. 1998, https://www.nature.com/articles/nm1298_1344

Itzhakim Ruth.”Herpes simplex virus type 1 and Alzheimer’s disease: increasing evidence for a major role of the virus.” frontiers in Aging Neurosciene, 11 Aug. 2014.http://pages.ucsd.edu/~mboyle/COGS163/pdf-files/Herpes%20simplex%20virus%20type%201%20and%20Alzheimer’s%20disease-increasing%20evidence%20for%20a%20major%20role%20of%20the%20virus-2014.pdf