Researcher Profile: Dr Timothy Couttas

BF: Your background is in chemistry rather than neuroscience –  tell me a bit about your early career and what drew you to medical research. 

TC: I’m a bioanalytical chemist by training. Driven by my background in analytical chemistry, I transitioned to biochemistry because I saw an opportunity to apply my skills to medicine.

After finishing my PhD at the University of NSW, I approached Professor Anthony Don because I believed I could translate those analytical skills into his research. That led to my first postdoctoral position, exploring changes in the human brain’s lipid composition and what those changes reveal about Alzheimer’s disease.

I fell in love with the project because it was an untapped way of approaching neurodegeneration, particularly Alzheimer’s disease. For decades, Alzheimer’s research has focused primarily on amyloid plaques and tau pathology. But even Alois Alzheimer himself noted changes in brain lipids when he first described the disease more than a century ago. Those observations never really came to fruition, and combining that idea with my analytical background felt like the right turning point in my career.

BF: In plain language, what is your research trying to understand?

TC: My research looks at fats, or lipids, in the human brain. Specifically, I’m building on findings around a class of lipids in myelin called sphingolipids. Myelin is the protective layer that insulates nerve fibres, much like the coating around an electrical wire, allowing signals to travel efficiently through the brain.

I believe an early biochemical shift destabilises how these lipids are packed together, causing myelin to break down and leaving nerve fibres exposed, creating conditions where Alzheimer’s pathology can take hold.

The Brain Foundation grant is allowing us to investigate whether these changes occur in human brain tissue. If they do, it could help us identify Alzheimer’s disease much earlier than is currently possible and open up entirely new opportunities for treatment.

BF: What’s been the most exciting finding so far?

TC: How striking the changes are in our preclinical models. I’ve never seen such consistent, defined changes at this stage of disease development.

We found these lipid changes emerging very early – before the classic signs of Alzheimer’s disease and before significant myelin breakdown occurs. That suggests we’re looking at one of the earliest biological changes in the disease process. 

Now we’re asking the critical question: do these same changes occur in people? That’s exactly what this Brain Foundation-funded study is designed to answer.

BF: Where does that work stand right now?

TC: We’re making real progress. In partnership with the Sydney Brain Bank, we’ve now completed analysis on approximately half of our human brain tissue cohort.

The tissue has been processed and analysed using mass spectrometry, and I can see the specific lipids I’m looking for very clearly. That’s really encouraging because it tells us the targets we’re interested in are there. What we don’t yet know is how they change across the different stages of Alzheimer’s disease. 

My honours student is currently running the second set of samples, and we’re hoping to have results by October or November this year.

BF: You’ve mentioned these lipids might be detectable in blood. What does that mean for patients?

TC: That’s what’s really exciting. In an earlier study, I looked at these same lipids in a group of people who each provided both blood and spinal fluid samples, and the changes between the two correlated almost perfectly.

That’s significant because one of the hardest things in neurological research is finding something that translates from the brain to the blood in a way that makes for an accessible, reliable biomarker. These lipids appear to do exactly that, and the mass spectrometry technology we use to detect them is already standard in pathology laboratories, with results available within 24 hours.

In the future, this approach could potentially become as routine as a standard blood test. That would represent a genuine shift – detecting Alzheimer’s disease before irreversible damage has occurred, rather than after.

BF: Does this research have relevance beyond Alzheimer’s?

TC: Absolutely. Take frontotemporal dementia, or FTD – it isn’t a single disease. It’s more of a spectrum, with genetic forms that look clinically similar but are quite different at the molecular level, and you can’t properly treat someone unless you understand that underlying biology. That complexity makes it harder to study, but it also means that understanding it better has the potential to teach us a great deal about neurodegeneration more broadly.

Traditionally, Alzheimer’s and FTD have been studied quite separately, but what my work and my collaborators applying the same technologies are showing is that they may share fundamental disruptions in how the brain handles lipids, particularly in myelin. The patterns differ in terms of which brain regions are affected and to what extent, but the underlying theme of lipid and myelin disruption appears to cross multiple neurodegenerative conditions.

What we find could serve not just as a diagnostic marker for one condition, but as a risk indicator or treatment target across many.

BF: I understand you’re also doing a lot of research in other areas of neuroscience, including schizophrenia. What else are you working on?

TC: Yes, that’s right. Schizophrenia is such a hard disease to get a handle on because, unlike Alzheimer’s, there’s no biological test whatsoever – diagnosis is entirely subjective. It’s still, as far as I know, the only major field of medicine without any real molecular understanding behind it.

I’ve been doing a lot of work in this space – setting up a new schizophrenia project, consulting for a pharmaceutical company in Germany on cannabis-based therapies, along with research into how microplastics affect brain and mental health and I’m also setting up a project on Parkinson’s Disease.

It all comes back to the same underlying question: what’s actually happening biologically?

BF: Is there a personal dimension that drives this work for you?

TC: If I’m honest, it goes back to high school when my mum was diagnosed with ovarian cancer. She’s absolutely fine now. They picked it up really early, so she didn’t need chemotherapy or anything like that. But it was my first real look into the science behind disease, what it means, and I guess it became a primary motivation for me.

Later, while I was already working in neuroscience, my grandmother, Nanny Mac, was diagnosed with dementia. I visited her in 2008 and she was completely herself: warm, present, and engaged. Just two years later, she could no longer recognise me or her own daughter. The decline happened so rapidly, and there was nothing anyone could do. Watching that occur, it’s just devastating.

BF: What do you want families living with dementia to know?

TC: We are moving beyond simply describing these diseases. We are starting to genuinely understand the underlying biology, and that progress is accelerating.

We’re no longer just studying end-stage disease. We’re examining the biological processes that occur years before symptoms appear, and those early changes could eventually become targets for treatment. 

We’re generating more data than ever before, thanks to advances in both analytical chemistry and computing, and that allows us to cross-reference findings across diseases, explore multifactorial changes we previously couldn’t, and move toward a more precision medicine approach.

The urgency is real – one in 10 people over 65 will develop some form of dementia, and by age 85 that rises to one in two. But so is the momentum.

I’d also say that research needs more than funding – it needs consumer and patient voices. Understanding what people living with these conditions want us to prioritise, whether that’s diagnosis, treatment or better ways to manage symptoms day to day, is just as important as the science itself.

There’s so much more to do, but I’m hopeful every day, as new ideas and technologies open doors to areas of research that weren’t even possible a few years ago. 

BF: How important is philanthropic funding, like the Brain Foundation grant, to making this happen?

TC: It’s hard to overstate. Government grants come with fixed timelines and defined milestones. If you don’t get there in time, the research stalls and the funding moves on. Philanthropic support offers something different – it provides longevity, allowing researchers to pursue ideas that may take years to yield results but could ultimately become the breakthrough.

Funding is deeply competitive, particularly for early- and mid-career researchers trying to establish a new area of research. The support that organisations like the Brain Foundation provide is invaluable, not just financially, but in terms of visibility and credibility as we work to build the case for our studies. Even when a project doesn’t produce the result we hoped for – every finding builds on the work of others.

Without continued investment, there are projects that never even see the light of day, and you just don’t know if that’s the one that could have changed everything. 

BF: Finally, what would you say to someone thinking about supporting brain research for the first time?

TC: It’s completely okay to feel uncertain. Get involved, learn more, ask questions and follow the research. By doing any of that, you’re already making a difference.

If you decide to contribute – whether financially, by sharing your expertise or simply by spreading the word – it all matters. Neurodegenerative diseases like dementia touch so many lives, and every contribution, no matter the size, moves us closer to the answers we desperately need.

Dr Timothy Couttas is a Research Fellow at Neuroscience Research Australia (NeuRA) and the Brain and Mind Centre at the University of Sydney. He is also a recipient of a Brain Foundation research grant. His Alzheimer’s research is conducted in partnership with the Sydney Brain Bank, and his current project’s co-investigators are Dr Claire Shepherd and Professor Anthony Don.