A researcher's journey
From the winter 2017 issue of Care and Cure magazine, read about a researcher's work in trying to develop a blood test for dementia.
Dr Elizabeta Mukaetova-Ladinska is a Clinical Senior Lecturer at Newcastle University and has completed an Alzheimer's Society-funded project to diagnose dementia by measuring proteins in blood.
'A dream does not become reality through magic; it takes… determination and hard work.'
When I started my clinical training in neuropsychiatry more than 30 years ago, dementia was not a hot topic in medicine. My late mother, Dr Milka Mukaetova, a GP working in a busy inner city practice, was instrumental in guiding me to start thinking about the mental health of older people, who represented the majority of her patients.
This coincided with one of the major discoveries in dementia research. My father, an economist with a passion for numbers and medical breakthroughs, was very excited when he tried to explain to me what 'A68' meant. 'A new protein that is clogging the brain, and hopefully there will be a cure for dementia soon,' he said, as he listened to Voice of America, at a time when Alzheimer's disease and dementia care did not make the news.
Little did I know at the time that the constituent of A68 would be the topic of my PhD, and I would continue to work on it for decades to come – measuring proteins extracted from the brain tissue of deceased people with dementia and understanding their clinical meaning so that I could use the knowledge in the care of my patients with dementia. More recently my research has moved on to developing a blood test for dementia.
Driven by questions
In doing so, I was driven by my patients I was seeing in the clinics.
'Isn't there a quicker way to diagnose my father?' relatives would ask me, as I was explaining the need for brain scans.
'There must be an easier and quicker way,' some would comment.
'Could a blood test help you know whether she has dementia or is just confused?' they would ask when discussing their mother's diagnosis.
Why do we not have a blood test for dementia? Or any simple test that could provide us with a diagnosis and help us begin treatment as soon as possible? Can we find similar changes to those we identified in the brain tissue of people with dementia in the other parts of the body, such as the blood, cerebrospinal fluid or skin?
Those were the questions that I also started asking myself, both as a neuroscientist and a clinician, while the first reports on blood proteins for dementia started emerging. These were all in plasma, the liquid in the blood that does not contain cells (red and white blood cells, or platelets, small blood cells involved in clotting).
Platelet cells found in the blood have certain similarities to the brain's nerve cells. Platelets contain many of the different proteins found in nerve cells, and in similar amounts. Our research has identified similar protein changes in platelets as those found in the brain tissue of people with dementia – tau protein (which forms the insoluble 'tangles' that cause brain cells to die), amyloid protein precursor protein (APP, which generates beta-amyloid and causes widespread 'plaques' in the brain), alpha-synuclein (which forms Lewy bodies) and other proteins that are involved in the neuronal cell death and inflammation.
We were also able to design novel methods to measure these proteins found within the platelets, and confirm that they change in people with dementia. Thus, tau protein increases in the early stages of memory problems, some are associated with agitation and aggression (such as clusterin and alpha-synuclein), whereas others reflect the progression of the memory problems (for example, APP) and use of anti-dementia treatments (immunoglobulins). These findings confirm further the complexity of the dementia process that can now be detected in the blood.
To the lab and back
What do these findings mean for people with dementia, their families and medical professionals? It is too early to claim that we have a blood test that we can use in our clinics to diagnose dementia. However the proteins identified in blood cells bring us closer to developing not only a diagnostic test, but also to differentiating between distinct forms of dementia, to monitor the progression of memory and behavioural changes, and to monitor the response to treatment using the currently available drugs.
With our engineering colleagues – Dr Eileen Yu and her team at the Department of Electrochemical Engineering, Newcastle University – we are developing a new way to provide a quick and reliable measure of blood proteins. This new technique has the potential to result in a hand-held tool that can be used in our clinics. We have expanded our research into other blood cells and are currently identifying new markers for dementia that we can use in new tests. Our aim is to have patient-friendly and inexpensive equipment that we can use routinely in dementia screening. This tool should be easily adapted to newly acquired knowledge about dementia risks, causes and treatments, and so facilitate the care and cure for people with dementia.
Over the last three decades, my professional work has been a marvellous and rewarding U-shaped journey from bedside to laboratory research and neuroscience, and back to the bedside. It was inspired by, in the words of the late psychiatrist Elisabeth Kübler-Ross, the 'most beautiful people we have known… those who have known defeat, known suffering, known struggle, known loss' – my patients, their families, carers and my own family. Without them, their natural curiosity and life stories, this research would have not happened.