New dementia research: How viral illnesses can damage future brain health

The search for a cause and cure for dementia has been frustratingly slow in comparison to the advances made in many other medical fields. There is a very good reason for this. Dementia often develops slowly over decades and is difficult to study in its early stages. You can’t easily take samples from the brain of a living person, for instance. And, since the brain is a dense and crowded place, even with advanced imaging techniques it is tricky to see exactly what is going on at a cellular level. So far, much of the research for Alzheimer’s has relied on using genetically modified mice or examining the brains of patients after their death.

“When you look at an Alzheimer’s brain, you see it at the very end of the road,” says neuro-engineer Or Shemesh. “You don’t know what might have happened 40 years ago which brought it to that state.”

Having a grandfather who developed Alzheimer’s and died in 2004 means the fight is a personal one for Shemesh. Based between the Hebrew University of Jerusalem and the University of Pittsburgh, he is working on creating new technologies to understand and treat brain disease.

Only about 1-2% of Alzheimer’s cases are caused by specific gene mutations. For the rest, something else must be going on. Shemesh is among a growing number of scientists who believe they may have identified what that something else could be. They have found a link between diseases of the brain and a number of common viruses, bacteria and fungi that are able to get inside it.

The blood-brain barrier is a layer of cells that is there to protect the brain, although it isn’t completely impenetrable. It allows small molecules to pass through, such as nutrients, and also some harmful pathogens. The thinking now is that these cause a protective inflammatory response that, in some people, can lead to cognitive decline later in life.

In the post-mortem Alzheimer’s brains that Shemesh and other scientists have been studying, a striking feature is the deposits of proteins known as tau tangles and amyloid plaques. “But these are downstream factors,” says Shemesh. “Something created them, and we believe it is pathogens.

“Until recently, this was considered a left-field hypothesis and was shunned. Now, the science is advancing and the community is accepting it more and more.”

Shemesh’s latest research used expansion microscopy to look for the virus that causes cold sores and genital herpes – known as herpes simplex virus-1 (HSV-1) – in post-mortem brains. There was plenty of it to be found. “We didn’t find a single person without herpes in their brain,” he says. “The difference between Alzheimer’s and non-Alzheimer’s brains, however, is how spread out it was. In a person who didn’t have Alzheimer’s disease it was here and there – less than a percentage of the entire image was taken up by the green particles that are the virus. In Alzheimer’s patients, it was way more spread out and the brain was full of HSV-1 proteins.”

The theory that emerges from the study is that the brain produces tau protein as a protective response to these pathogens in the short term but, just like inflammation in the rest of the body, if it gets out of control and becomes chronic, then it starts to cause damage.