Dr Marc Aurel Busche is a Group Leader at the UK Dementia Research Institute at UCL and Honorary Consultant Psychiatrist at Queen Square National Hospital for Neurology and Neurosurgery.
What attracted you to the area of dementia research initially?
What initially attracted me to dementia research was my strong interest in medicine and neuroscience.
During my medical studies in Munich, I spent a year in Arthur Konnerth's laboratory, where I learned about two-photon microscopy and its application in imaging living brains.
My fascination grew when I applied my new skills to study an Alzheimer's model and made a surprising and completely unexpected discovery: nerve cells surrounding amyloid plaques – a hallmark of the disease – exhibited abnormal hyperactivity, contrary to previous assumptions.
As my understanding of the field deepened, I recognised a substantial gap in knowledge concerning the effects of Alzheimer's pathology on brain function. Although much was known about the genetics and pathological proteins implicated in the disease, the actual processes taking place within the brain were still largely uncharted territory.
This realisation inspired me to continue research on Alzheimer's pathophysiology, while simultaneously pursuing a psychiatry residency to acquire a more comprehensive understanding of the clinical aspects of dementia. This combination of basic research and clinical work has been a driving force in my career, enabling me to bridge the gap between scientific discoveries and their potential to positively impact patients' lives.
You are leading a major UK DRI Grand Challenge project focused on developing a functional circuit biomarker for Alzheimer’s disease. Can you tell us more about this?
Alzheimer's disease starts to develop years, or even decades, before the first symptoms appear. Based on the latest clinical trials, it is becoming increasingly clear that treatments will likely be most effective if we can administer them early in the disease's progression, before extensive damage to the brain occurs.
To do this, we need to find biomarkers that can detect the disease at an early stage and help us monitor how well therapies are working. In our research over the past few years, we've found that brain cell activity changes very early in response to Alzheimer's pathology.
So, our Grand Challenge Project, which is made possible by the unparalleled clinical and neuroscience expertise available at UCL, aims to detect these initial functional changes in the human brain, even before symptoms arise, by employing magnetoencephalography (MEG) in tandem with machine learning.
We're also leveraging cutting-edge neuroscience technologies such as two-photon imaging, optogenetics and Neuropixels in disease models to decipher the critical underlying cellular mechanisms and explore novel therapeutic targets.
It's an exciting collaboration involving several groups at UCL, including those led by Ray Dolan and Nick Fox, as well as David Dupret's team at the University of Oxford. We're incredibly grateful for the support we've received from the UK DRI for this project, and we hope that our work will bring us closer to effective early detection and intervention for Alzheimer's.
What aspect of your work most excites you and why?
What truly excites me about the work we're doing is the potential for multiple aspects of our research to make a significant impact. Alzheimer's is among the most pressing challenges our society faces today, akin to the climate crisis or sending people to Mars.
Tackling this complex problem not only helps us better understand this devastating disease and accelerate the development of successful therapies, but also provides valuable insights into the broader workings of the human brain, another monumental scientific frontier.
I feel incredibly fortunate to lead a laboratory where an exceptionally talented team of postdocs and students are conducting fundamental research on Alzheimer's, work that could potentially benefit patients in the future. At the same time, I'm also taking care of patients, which adds a unique dimension to my work.
This balance between providing immediate help to patients and working on long-term solutions to improve their lives in the future is perhaps the most fascinating and rewarding part of my job. As I mentioned earlier, the ability to bridge the gap between scientific discoveries and their potential impact on patients' lives serves as a driving force that keeps me passionate about my work.
What would you say to someone who is considering whether to study neuroscience at UCL?
UCL's exceptional strength in neuroscience is what initially attracted me. It is undoubtedly one of the world's top institutions for neuroscience research. Students benefit from access to cutting-edge resources, such as state-of-the-art laboratories, advanced instruments, and collaboration with leading researchers.
What truly sets UCL apart is its unique combination of research depth and breadth, paired with a collaborative atmosphere and flat hierarchies. This nurturing environment encourages interdisciplinary connections, allowing students to work closely with top experts, expand their perspectives, and enrich their overall learning experience.
What’s the best advice you would give to a younger self?
If I were to give advice to a younger self, I'd say not to get too caught up in chasing after the ‘hot’ topics of the moment, but instead, follow your intellectual curiosity. When I began my research journey, I was initially interested in learning state-of-the-art neuroscience techniques without being tied to a specific disease or subject. This open-mindedness allowed me to apply my skills where I could make the most impact and develop a niche for myself, which I believe is crucial for success in academia.
It's also essential not to feel intimidated and to take risks. I remember when I started out as a medical student, I wasn’t really qualified to do research and didn't even know how to use a pipette. But within a few days, I was operating a two-photon microscope worth half a million or so. I learned that motivation, persistence, and curiosity to learn new things are far more important than having all the answers or expertise from the beginning. Embrace the learning process and trust in your ability to grow and adapt.