Viruses Causing Neurodegenerative Diseases

Fifteen years ago, Harald zur Hausen was awarded the Nobel Prize in Physiology or Medicine for discovering the links between viruses and cancer. It took decades to provide evidence that the human papilloma virus can cause cervical cancer. Recently, several new studies have found that viruses could also be the culprit behind neurodegenerative diseases.

Future Pandemics

Neurodegenerative diseases (ND) are set to become a major challenge in medicine in the near future, as most of these diseases are associated with older age. With the demographic shift taking place in many countries, an estimated 1 in 6 people worldwide will be over the age of 60 in 2030. The most prevalent ND is Alzheimer’s Disease (AD), which affects an estimated 24 million people globally. Past the age of 65, the incidence of AD doubles every five years, affecting nearly a third of adults by the age of 85.

The second most common ND is Parkinson’s disease; around 10 million people currently have the disease. And while recent decades have seen huge progress in heart disease and cancer, there are still no treatments for ND.

Slow Viruses

Historically, there were many indications that certain viruses could cause ND. Those who were exposed to the Spanish flu outbreak of 1918 had a higher risk of developing Parkinson’s disease in later life.

It has long been known that the varicella zoster virus, a herpes virus that frequently causes shingles in older adults, can result in neurological complications. In the 1950s, herpes was also associated with AD, as it was supposed that these types of “slow viruses” can, with time, cause irreversible damage to the central nervous system. In 1982, Ball and colleagues demonstrated that similar parts of the brain are affected by herpesviral encephalitis and AD, and symptoms for both illnesses, such as memory loss and cognitive function, are comparable.

Since the 1980s, research in ND has been more focused on the outcomes of disease progression, such as the accumulation of insoluble proteins in the brain in AD, but in the past few years there has been a scientific turnaround to the earlier theories.

The Power of Data Science

The studies that demonstrated connections between viral illnesses and the onset of ND later in life were based on monitoring very large groups of people for a certain amount of time (cohort studies) or by extracting information from medical records. One study looked at over 265,000 patients infected with the herpes virus in Sweden over a 12-year period and determined that if untreated, the virus increased the risk of dementia by 50%.

In 2022, a study that monitored over 10 million US military personnel for over 20 years came up with the astonishing result that almost every soldier diagnosed with multiple sclerosis was previously diagnosed with the Epstein-Barr virus, also a herpes virus, which is very common.

Another study, published earlier this year, analysed data from the FinnGen project, a biobank containing data from more than 300,000 people in Finland, and found 45 associations between viruses and ND. Researchers then compared the results with data from the UK biobank, containing medical records of over 500,000 people and confirmed 22 of the associations. Most significantly, patients with viral encephalitis were 30 times more likely to suffer from AD in later years. The flu virus with pneumonia was found to increase the risk of several types of ND, including AD and Parkinson’s disease.

A Viral Infection Is Just One Factor

The knowledge that infections are a risk factor for ND is a great step forward, but future research will have to come up with answers as to why this is so. There are hypotheses that infections trigger the activation of immune cells in the brain, and the resulting inflammation, intended to protect the brain, ends up causing damage to the nervous system. The molecular mechanisms that determine the role of viruses during and after infection are still unclear.

Does this mean anyone who falls ill with pneumonia or a herpes virus will eventually have to face a neurodegenerative disease? It isn’t that simple. Just as viruses do not cause cancers on their own, the onset of ND is developed through a combination of factors − a person’s genes, environment, and lifestyle.

The results of these studies put the importance of prevention and treatment of viral illnesses in perspective; it isn’t just the short-term infection that should be managed, but also possible future outcomes. For example, a large study of Americans over the age of 65 found that those who received at least one influenza vaccine were 40% less likely to develop AD during a 4-year period.

There may be no direct treatment for ND just yet, but we may already have viable methods of reducing the risk factors.