A NEW WAY TO TRACK BRAIN DISEASE AND INJURY

Early career researcher Dr Helen Murray is doing extraordinary things with brain tissue and a technique called multiplex labelling.

“We can now get more information from a single slice of tissue than ever before, and we can get it more quickly. That gives us powerful ways to learn more about brain diseases such as Alzheimer’s and repetitive brain injury often seen in sportspeople,” says Murray.


She is a postdoctoral research fellow at the Centre for Brain Research at the University of Auckland and holds a concurrent non-clinical collaborator appointment in Dr Alan Koretsky’s lab at the National Institutes of Health (NIH) in the USA.


Murray completed an Honours project with Sir Richard Faull on a Huntington’s sheep model and a PhD with Professor Maurice Curtis looking at plasticity in human Alzheimer’s disease brains. She then split her research efforts between New Zealand the US, returning here full-time in 2020 to establish a research programme studying the pathology of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with repetitive head injury in sport.


Tissue analysis is a critical part of understanding brain disease and injury. During her PhD studies, Murray learnt to preserve tissue, prepare ultra-thin slices for study and how to apply very specific fluorescent labels that would bind to only one part of the tissue she wanted to study.


“I focused on Alzheimer’s and a protein called Tau. The disease causes the tau protein to clump and form dense tangles inside cells. The more tau in the tissue, the greater the brain damage.”


Top row: A sample of normal brain tissue (left), alongside samples showing mild and severe CTE. The brown stain indicates tangles of tau protein. Defective tau is associated with CTE and Alzheimer’s disease. The bottom row shows microscopic images of tau, stained red, embedded in brain tissue.

Photo by Ann McKee. She is the leading researcher on CTE in Boston, USA, and runs the world’s largest CTE brain bank.



“We see this tangle pathology in both Alzheimer’s and CTE, but the difference between the two is where the Tau accumulates in the brain and how it moves around,” says Murray.


“In Alzheimer’s, we see Tau tangles in the part of the brain involving memory; in CTE, they form in the deep valleys between the folds of the brain, areas experiencing the most stress in a head knock. If you think of sportspeople such as boxers, and repeated blows to the head, you get an idea of the forces experienced by the brain during a knock.”


Her current focus is finding biomarkers to diagnose CTE in living people which means finding out what’s happening in the brain at the start of the disease. “We don’t know a lot about CTE. For example, what’s the tipping point? Why do some people playing contact sport develop CTE and others don’t? How can we modify, delay or prevent this disease? The first step to answering any of these questions is to figure out what’s actually happening in the brain.”


While working at the NIH, she was part of a team that developed a method to label up to 100 proteins in brain tissue with different fluorescent tags, essentially ‘painting the brain’ with multiplex fluorescent labelling.


From L-R. different types of brain cells, the highways of brain cell connections, and blood vessels on the same slice of tissue.

Photo: Helen Murray, Centre for Brain Research, University of Auckland and Dragan Maric, National institutes of Health, USA.


“This multiplex immunohistochemistry has given us incredible images where we can see all of the complex and fine detail in the brain tissue. Rather than seeing just one marker of a blood vessel, I can see all the different layers and whether there’s a specific part of that blood vessel that has changed. This means we get at least 20 times more information from a single piece of brain tissue than in the past.”


Murray has now built a broad team of international and domestic collaborators to develop new analysis pipelines for the technique. “Over the next year or so, I want to keep that momentum going and create the first CTE neuropathology programme in New Zealand. This work will happen alongside the new sports brain bank initiative as part of the Neurological Foundation of New Zealand Human Brain Bank”.


“I also want to look at what we can do outside the human tissue space – engaging with the community, talking to clinicians about biomarkers.”


Her long-term vision is to develop multiplex immunohistochemistry for both her CTE research and as a collaborative platform.


There is an obvious question here: how do you track brain tissue injury like CTE in living people? “We’re working with the Centre for Brain Research to see what’s possible, because we know that these injuries can take years to emerge and are often only discovered after death.”


She is supported by the Healthtech Capability Programme (HTCP) which is part of Te Titoki Mataora MedTech Research Translator, a multi-faceted initiative focused on growing Aotearoa New Zealand's deep tech sector by supporting research and industry that address healthcare needs.


Listen to Dr Murray talking about the relationship between repetitive head injuries and dementia. This talk was given during the University of Auckland’s ‘Raising the Bar Home Edition’.