Vaccines and Neurodegeneration: Lessons for Huntington’s Disease?

A recent article in the scientific journal, Nature describes “A natural experiment on the effect of herpes zoster (shingles) vaccination on dementia”. This study makes similar conclusions to other studies worldwide, and was based on a regulatory phenomenon in Wales, UK, in which depending on a precise birth date in 1933, people could receive a free herpes zoster (shingles) vaccine, or not, even with birthdays a week apart from each other. This led to two very distinct groups of people who were about the same age: almost all vaccinated versus almost none vaccinated. Then a simple question was asked…  

Is there any difference in dementia incidence between these two groups of people?

The answer was a clear yes, by 20%, and the predominant effect was in women, a component that is not understood yet. Incredibly, this would make the shingles vaccine more effective at reducing Alzheimer’s disease incidence than any recent FDA-approved drug. But why? Does shingles cause Alzheimer’s? What about other common vaccines? Do they have any effect? 

This question has been asked in so many studies worldwide, it’s best at this point to refer to analysis of many studies, or meta-analyses, which compare all the data on an even ground. The conclusion across many studies is similar: influenza, pneumonia, as well as tetanus, diphtheria, pertussis (dTAP) vaccines all reduce risk of developing Alzheimer’s and the more broadly defined dementia. 

So, if it’s not any one virus, or bacteria, then how can so many different types of infection contribute to neurodegeneration? And how do vaccines reduce the risk of developing these brain diseases? 

Vaccines can help even after infection

Chicken pox infections took place in most children prior to the common use of varicella vaccine in the late 90s. While people were told for decades that they cannot get the virus again, the reality is that their immune systems learned how to control the virus for the rest of their lives. The virus never goes away, and it remains dormant in the nervous system. 

If there is a period of an immune compromising event, like illness, aging, or chemotherapy, people can see the zoster virus re-activate leading to the condition of shingles, which is painful because the virus is in sensory neurons and in skin. So the best advice for those infected once with chicken pox is to take the two dose vaccine later in life to prevent shingles by keeping the immune system primed to control the virus.

But is this relevant to HD?

These studies aren’t just about dementia. As well, there are observed lower incidences of Parkinson’s disease in those who were vaccinated. There has been a classic connection between influenza infections and onset of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, another progressive neurodegenerative disease with genetic origins that is often seen triggered by something called a “redox imbalance.”  

A redox imbalance refers to high levels of toxic byproducts of cellular metabolism, called reactive oxygen species (ROS), reactive sulfur species (RSS), or reactive nitrogen species, that are essentially the pollution in cells as a result of burning energy. It’s in these toxic reactive byproducts that lies the clues to the efficacy of vaccines against neurodegeneration. 

The response to infections, most infections, is inflammation, where the soldiers of the immune system can use potent blasts of ROS to wipe out bacteria and viruses. In the aftermath, in young, healthy people, the brain’s cellular powerhouse (the mitochondria) can clean up those reactive byproducts and allow recovery from inflammation. 

However, two events can prevent this response to bacterial or viral invaders from happening in people: 1) an underlying genetic disease, such as HD, which is known to affect mitochondria, 2) and/or human ageing, as all humans lose mitochondrial efficiency with age. This impact on mitochondria lowers their ability to lower ROS. 

In HD, particularly later in life, we have both situations, which makes inflammation, like that caused by infections, dangerous. It’s particularly a problem in the brain because brain cells are very active, burning a tremendous amount of energy, even at rest, and a byproduct of all that burning is ROS.

The take home message

While there is no vaccine that is claiming to prevent neurodegeneration, these correlations between vaccination and lower disease risk may be important. At this point, there are not published studies on the protective effect of vaccines in HD and this information is not yet captured in the ENROLL-HD study. 

However, it is prudent to suggest that those with HD or those who are gene carriers avoid any viral or bacterial infections through the use of vaccines and good hygiene habits we were all reminded of during the onset of COVID-19.

Summary

• Multiple vaccines (shingles, flu, pneumonia, dTAP) are associated with 20% reduced dementia risk, which data suggests is more effective than recent Alzheimer’s drugs
• Effects are seen across Alzheimer’s, other dementias, and Parkinson’s disease
• Infections trigger inflammation and produce toxic cellular byproducts (like reactive oxygen species) that healthy mitochondria normally clear
• In HD, mitochondria are already impaired and struggle to handle inflammation from infections
• Aging also reduces mitochondrial efficiency, creating double risk for people with HD later in life
• Brain cells are especially vulnerable due to high energy use and resulting toxic byproduct production
• Bottom line for HD community: Stay current on vaccines and practice good hygiene to avoid infections that could stress already-compromised mitochondria

Acknowledgments

We thank Dr. Dr. Caitlyn Mullarkey, Dr. Matthew Miller, and Dr. Dawn Bowdish from McMaster University in Toronto, Canada for their input on this article.