Alzheimer’s Disease Research Goes Viral

When the brains of people who have been diagnosed with Alzheimer’s disease are examined, clusters and tangles of two proteins, amyloid and tau, are observed.  It has long been assumed by most experts that the disease is caused by these protein clusters interfering with neural function.  Research on this path focused on decreasing the accumulation of these proteins in the brain. However, progress has been small, and it has not yet determined whether amyloid and tau are a cause or an effect of the disease.  An article in The Economist, Do viruses trigger Alzheimer’s?, summarizes some recent discoveries that support the possibility the disease could be activated by viruses. 

“In the summer of 2024 several groups of scientists published a curious finding: people vaccinated against shingles were less likely to develop dementia than their unvaccinated peers. Two of the papers came from the lab of Pascal Geldsetzer at Stanford University. Analysing medical records from Britain and Australia, the researchers concluded that around a fifth of dementia diagnoses could be averted through the original shingles vaccine, which contains live varicella-zoster virus. Two other studies, one by GSK, a pharmaceutical company, and another by a group of academics in Britain, also reported that a newer ‘recombinant’ vaccine, which is more effective at preventing shingles than the live version, appeared to confer even greater protection against dementia.”

Kudos go to Professor Ruth Itzhaki who long ago detected a potential correlation between a common virus that infects much of the population, but rarely infects the brain, and Alzheimer’s.  She observed that when the virus does manage to infect the brain it can cause severe inflammation in regions that are sites for Alzheimer’s disease damage.

“Ruth Itzhaki, formerly of Manchester University and now a visiting professor at the University of Oxford, has championed this idea for almost 40 years. The bulk of her work has focused on herpes simplex virus 1 (HSV1), best known for giving people cold sores, which infects around 70% of people, most without symptoms. The virus normally lives outside the brain, where it can lie dormant for years. It is flare-ups that can lead to cold sores.”

“In rare cases, the virus can also lead to massive inflammation in the same brain areas that are most affected by Alzheimer’s. In experiments conducted in the early 2000s, Professor Itzhaki found that if she infected lab-grown human brain cells with HSV1, amyloid levels inside the cells increased dramatically. That led her to suspect a causal connection.”

“What’s more, in 1997 Professor Itzhaki found that people with a genetic variant known to increase Alzheimer’s risk, ApoE4, were only more likely to get the disease if they also had HSV1 in their brain. In 2020 a group of French scientists showed that repeated activations of the virus, seemingly harmless in people without ApoE4, more than tripled the chance of developing Alzheimer’s in those with it.”

One would have hoped that Itzhaki’s research would have generated interest much earlier.  Now the medical researchers are struggling to catch up.

“In a bid to push forward Professor Itzhaki’s theory, a group of 25 scientists and entrepreneurs from around the world have assembled themselves into the Alzheimer’s Pathobiome Initiative (AlzPI). Their mission is to provide formal proof that infection plays a central role in triggering the disease. In recent years their work detailing how viruses trigger the build up of proteins linked to Alzheimer’s has been published in top scientific journals.”

Evidence of a tie between the shingles virus and the HSV1 virus has now been observed.

“Researchers at Tufts University, working with Professor Itzhaki, have probed why such reactivation occurs. In 2022 they found that infection with a second pathogen, the shingles virus, could awaken the dormant HSV1 and trigger the accumulation of plaques and tangles. This may explain why shingles vaccination appears to be protective against dementia. In another study published in January, the Tufts researchers also showed that a traumatic brain injury—a known risk factor for Alzheimer’s—could also rouse HSV1 and start the aggregation of proteins in brain cells grown in a dish.”

If this viral hypothesis proves valid, it is fantastic news for those who fear a long decline into dementia, and those who are already experiencing that decline.  Viruses can be controlled by vaccinations and by antiviral drugs, potentially eliminating future disease and limiting current disease.

“The viral theory has promising implications for treatment. Current therapies for Alzheimer’s, which attempt to reduce levels of amyloid in brain cells, merely work to slow the progression of the disease. If viruses are a trigger, though, then vaccination or antiviral drugs could prevent future cases. Such treatments could also slow or halt the progression of Alzheimer’s in those who already have the disease. None of this requires major breakthroughs. Antivirals for the cold-sore pathogen already exist and are off-patent. And the shingles vaccine is now routinely offered to elderly people in many countries.”

“Around 32m people around the world are living with Alzheimer’s disease. If antiviral treatments can indeed slow, delay or prevent even a small subset of these cases, the impact could be tremendous.”

You can learn a little about a lot of things or you can learn a lot about a very few things. Guess which is the most fun.