Although I always knew I wanted a career in research, if you had asked me as an undergraduate student what I wanted to research, I would have had no idea. I was first introduced to neuroscience during my undergraduate courses. Lectures where we learned about the brain were of particular interest to me, and this interest grew during my summer studentships in Christchurch. I had now narrowed down my field of study to the brain, but still had no idea what specific part of this complex organ I would like to research.
I used to think the brain was just a mishmash of neurons but now most of my research is on pericytes, a cell I had never heard of when I decided I wanted to pursue neuroscience research. Pericytes are cells that wrap around the cells that line the small blood vessels in the body. Pericytes maintain the blood brain barrier, clear out debris, and regulate the immune response. The blood brain barrier is particularly important for brain health because it acts as a filter to keep harmful things out of the brain. It was during my time working with Professor Mike Dragunow that I became interested in pericytes. His team had just developed a new method for growing pericytes from human brain tissue and were really interested to see if these cells played a role in the development of Alzheimer’s disease.
I am most interested in the pericytes and the blood vessels in the brain because there are 600 kilometers of blood vessels in the human brain. This provides a huge surface area for interaction between the brain and the rest of the body. All blood vessels are lined by endothelial cells, and the pericytes wrap around these cells. Both endothelial cells and pericytes are affected by the normal aging process and Alzheimer’s disease, and contribute to the neuroinflammation that drives Alzheimer’s disease. My current work examines the interaction between blood vessels and our most abundant white blood cell, the neutrophil. We believe this might be important in Alzheimer’s disease as well as other brain diseases. We have found that neutrophil proteins accumulate around plaques in Alzheimer’s disease, and that blood vessels encourage them to release this protein. Furthermore, oxidative stress resulting from these neutrophils can cause pericytes to die. The abnormal cell death that results causes further inflammation. We think that neutrophils might therefore be an important, and underappreciated, contributor to Alzheimer’s disease through their effects on blood vessels.
The ultimate goal for any researcher is of course, to make a discovery that directly impacts quality of life. During Alzheimer’s disease plaques form in the brain. Most current drugs that are being trialled target the protein that forms these plaques, but these trials have failed. This does not mean that the plaques are not important in the development of Alzheimer’s disease, they are. The problem is that by the time most people receive the drugs the disease has progressed to a stage where the symptoms are independent of the number of plaques. I hope that targeting some of the other processes that cause neuroinflammation might be more successful. If people could begin treatment earlier, they would see a greater reduction in symptoms, and extend the time they can live a normal life.
It is fulfilling to go to work every day and know that I am playing a part in something that could not only help people, but be life changing. Biology doesn’t have many ‘hard’ rules like physics or chemistry, so it’s very hard to predict what you might find. That makes my work all the more rewarding when you make that very first discovery and you see the possibilities and implications it has for your field of work. Then comes the hard part of testing all those possibilities.
I am extremely grateful to the Neurological Foundation and all of the supporters who provide much needed funding to researchers. Securing funding for health research in New Zealand is very challenging, and during a year like 2020 there is even less money than usual to go around. Without the generosity of the Neurological Foundation and its supporters, many scientists like myself would simply be unable to pursue important research. I feel very privileged that the Neurological Foundation have chosen to fund my research.
If I could say one thing to the people reading this article who are considering donating to the Neurological Foundation, it would it be, research changes lives. Consider all of the drugs, and medical procedures we now take for granted that save lives every day. They would not be possible without research. Just in my field alone, basic science research is close to providing blood tests to diagnose Alzheimer’s disease. Although research seldom responds in predictable ways, over time the benefits are immeasurable.
I think that now is the most exciting time to be a researcher. We know so much more about the brain than we did even a decade ago, and we have such amazing tools to understand it. I am excited to see the promise of this research come to fruition, and the success of new therapies we will have 50 years from now.