How to prevent Alzheimer’s disease: a case for vaccines

According to the World Health Organization, there are approximately 10 million new cases of Alzheimer’s disease and other forms of dementia worldwide each year. That corresponds to approximately 1 new case every 3 seconds. As demographic shifts allow people to live longer, the total number of people living with this disease is expected to double over the next twenty years. Emerging research now shows that vaccination against common viruses can significantly reduce the risk of developing Alzheimer’s disease.

Alzheimer’s disease is characterized by the accumulation of beta-amyloid plaques and tau neurofibrillary tangles that ultimately lead to brain atrophy or shrinkage. Changes in the brain often begin years before the onset of cognitive symptoms, making this a particularly challenging disease to diagnose and treat. The pattern of structural damage observed in the brains of people with Alzheimer’s disease shows signs of significant neuroinflammation. High levels of inflammation in the brain over several years can be both a cause and a consequence of developing this disease.

Inflammation in the brain can occur when you are exposed to a virus. Even without directly infecting brain cells, viruses are able to induce such a strong inflammatory response that it overwhelms the entire body. The Covid-19 virus, for example, is particularly adept at eliciting a robust immune response. In some cases, damage to the brain caused by inflammation can persist even after symptoms have resolved.

However, certain viruses never completely leave the body. For example, when a person is exposed to the varicella-zoster virus that causes chickenpox, some of the virus becomes latent and remains in the body. Latent viruses can lie dormant for years, even decades, without replicating in the body before reactivating. Reactivation of a latent virus initiates a new infection and triggers an inflammatory response. After a chickenpox infection, the virus reactivates in one in three people and presents as shingles, a painful rash.

There are increasing reports that exposure to chickenpox and subsequent reactivation of shingles may be linked to Alzheimer’s disease. In brain tissue samples, researchers have observed that exposure to the varicella-zoster virus causes the formation of beta-amyloid aggregates and aberrantly phosphorylated tau, which resemble the amyloid plaques and neurofibrillary tangles characteristic of Alzheimer’s disease. Administration of chickenpox-targeted antiviral agents significantly reduces the accumulation of beta-amyloid and phosphorylated tau. These findings reveal a possible mechanism for how Alzheimer’s disease develops, and more importantly, how it can be prevented.

How can exposure to the chickenpox virus cause Alzheimer’s disease so much later in life? One theory holds that the latent varicella-zoster virus is continually reactivated in response to stress, leading to cumulative damage in the brain over time. In this way, the presence of the reactivated virus directly causes the formation of amyloid and tau aggregates in the brain. However, this theory is limited by previous reports that reactivation of the varicella-zoster virus occurs only once and causes shingles.

Considering that Alzheimer’s disease develops over decades, new study from the University of Oxford suggests that this virus likely has an indirect effect by increasing inflammation in the brain. The team speculated that reactivation of the chickenpox virus develops into shingles only in severe cases. An inflammatory response to the newly activated virus then triggers a cascade of additional neuroinflammation that damages brain cells.

In this study, Cumin et al. began by obtaining human stem cells that resemble brain tissue. These cells were then exposed to the varicella-zoster virus. Although they did not observe the formation of beta-amyloid and tau proteins, researchers measured increased levels of pro-inflammatory cytokines, confirming their hypothesis that the correlation between chickenpox and Alzheimer’s disease may be indirectly caused by inflammation. Cumins et. al concluded that the proinflammatory cytokines activated by varicella-zoster virus can cause recurrent reactivation of latent viruses, ultimately leading to the development of Alzheimer’s disease.

These findings are consistent with clinical reports that vaccination against chickenpox and shingles can significantly reduce the risk of Alzheimer’s disease. Vaccination against other common viruses, such as influenza, has been shown to have a similar protective effect. a recent research published in the Journal of Alzheimer’s found that getting one flu vaccine can reduce the risk of developing Alzheimer’s disease by 40% in people over age 65.

Although the mechanism of how inflammation leads to Alzheimer’s disease is not yet clear, getting your vaccinations on time offers some protection. We are just beginning to understand the role the immune system plays in Alzheimer’s disease. This is not an isolated brain disease. Clearly, environmental factors and lifestyle choices that increase your vulnerability to encephalitis can put you at risk for developing this and other forms of dementia.