Mary Paraskevaidi is a Postdoctoral Research Associate at the University of Central Lancashire (UK) and Imperial College London (UK) and is working in the field of disease investigation and diagnosis with the application of analytical chemistry techniques. She completed her PhD in Biomedical Sciences at Lancaster University (UK) and the University of Central Lancashire, during which she developed an interest in translational research and neurodegenerative disorders.
In this interview, Mary speaks to us about her research using spectroscopic methods to detect Alzheimer’s disease (AD) in blood plasma – a technique that she mentions has demonstrated accurate diagnosis of not only AD patients in advanced disease states, but also those with very early symptoms.
1.Could you tell us more about the talk you were supposed to be giving at the Alzheimer’s Research UK Conference (17–18 March 2020, Newport, UK) on emerging concepts in dementia research?
It was with great sadness to find out that ARUK 2020 had to be cancelled, as it would have been a great opportunity for experts in the Alzheimer’s field to come together and share their research. However, growing concerns over COVID-19 rendered its cancellation necessary and people should really act responsibly and take the right precautions against this unprecedent situation.
With regards to the talk I would give at the conference, we have performed a substantial amount of work in the field of AD in an effort to develop a new blood test that could be utilized for an accurate and timely diagnosis.
“What we propose as an alternative approach is the use of a spectroscopic technique, which can be used to analyze a biological sample and provide information for a range of different biomolecules (e.g., proteins, lipids and carbohydrates), rather than focusing on individual biomarkers.”
AD is a complex, multifactorial disorder with a number of genetic, epigenetic and environmental factors playing an important role in its development and progress, ultimately leading to premature neuronal death.
With a rapidly aging population across the world, AD is expected to affect approximately 75 million people in 2030, which necessitates, now more than ever, an early and accurate diagnosis. An early diagnosis is expected to expedite the recruitment of patients into clinical trials as well as the prescription of promising drug candidates, before severe brain damage occurs.
Currently, an accurate diagnosis remains challenging and is based on clinical presentation as well as imaging and biofluid biomarkers, such as those derived from cerebrospinal fluid (CSF) and blood. Specific CSF markers have been shown to have optimal diagnostic accuracy, however, the nature of their collection is invasive, which limits their wider use in routine clinical practice.
Over the last decade, and with the advent of sensitive analytical technologies, there is emerging evidence that blood could serve as an information-rich sample for AD diagnosis. Different blood biomarkers, such as amyloid-β, tau and neurofilament light, have shown promise.
What we propose as an alternative approach is the use of a spectroscopic technique, which can be used to analyze a biological sample and provide information for a range of different biomolecules (e.g., proteins, lipids and carbohydrates), rather than focusing on individual biomarkers. This approach is anticipated to be beneficial for more accurately detecting multifactorial diseases, such as AD or cancer.
In summary, in my talk I would discuss the use and advantages of such technologies in the field of AD and also present some of our results on this.
2.Part of your work focuses on the detection and early diagnosis of neurodegenerative diseases using biological fluids – can you tell us more about this? What advancements have been made in the field?
“It is also worth noting that we managed to accurately diagnose not only AD patients in an advanced disease state, but also those who had very early symptoms, a fact which is critical as it would allow an early intervention.”
There is an intensive effort from numerous research groups to develop effective AD tests using biological fluids. As already mentioned, the use of CSF – even though clinically used in many parts of the world – is not ideal, as it requires an invasive and painful sampling procedure that is rarely performed by general practitioners. Therefore, a lot of focus has been placed instead on the study of blood as a minimally invasive and easily collected alternative sample.
As part of my research, I have looked into spectroscopic methods with regards to detecting AD in blood plasma. Spectroscopy exposes a sample to electromagnetic radiation, which causes characteristic chemical motions of the biomolecules within the sample, therefore allowing generation of specific patterns, known as ‘biological fingerprints’. Altered ‘fingerprints’ emerging from an existing disease can thus be used as a diagnostic tool when compared to those from healthy individuals.
Blood spectroscopy has been used in our studies to compare individuals with AD, as well as other dementias, to healthy volunteers serving as the study’s controls. The diagnostic accuracy (sensitivity and specificity) achieved by this test was comparable to, if not better than, other currently used tests, while at the same time it has the advantage of being inexpensive, fast and simple as a method, without the need for laborious assays or costly reagents.
“In addition, this blood test differentiated AD patients from patients with another common subtype of dementia, known as dementia with Lewy bodies, a crucial distinction for providing a more accurate prognosis and administering a suitable treatment.”
It is also worth noting that we managed to accurately diagnose not only AD patients in an advanced disease state, but also those who had very early symptoms, a fact which is critical as it would allow an early intervention. In addition, this blood test differentiated AD patients from patients with another common subtype of dementia, known as dementia with Lewy bodies, a crucial distinction for providing a more accurate prognosis and administering a suitable treatment.
This work has great potential to be developed into a minimally invasive, cost-effective blood test for the differential diagnosis of AD. Further future research should aim to establish whether the proposed approach could also detect individuals at a pre-symptomatic phase and whether this method could serve as a screening test in high-risk cohorts. As a future direction we aim to study buccal cells as a potential non-invasive source of AD biomarkers.
3.How close are we to seeing this translated into the clinic? What obstacles are yet to be overcome? In your opinion, how might these challenges be addressed?
Translation into the clinic would require further follow-up clinical trials in larger number of patients in order to replicate and confirm our initial results. Assuming results of these trials show non-inferior or even superior accuracy to that of existing tests, that would permit further introduction of these methods into clinical practice. I believe that clinical translation would require a number of years. Also, prospective studies should focus on the recruitment and investigation of pre-symptomatic individuals to demonstrate the efficacy of the method as a screening tool.
Some of the obstacles that have hindered clinical implementation so far include lack of standardization of techniques and sample preparation, as well as lack of large-cohort multicenter studies, all of which are necessary to validate results before novel methods are used as part of life-changing decisions within a clinical environment. As with every analytical technique for diagnostics and/or biomarker discovery, many requirements and phases (pre-analytical, analytical and post-analytical) need validation in independent datasets and by independent researchers before clinical approval.
Blood spectroscopy has the potential to be translated from a laboratory-based tool to a necessary and informative clinical tool. Continued development towards automation of technological processes, in combination with the advent of portable, clinic-based instruments, will undoubtedly facilitate large-scale studies in the years to come.
4.Lastly, what developments are you most excited to see in the field of dementia in the next 5–10 years’ time?
“I am personally hopeful for the future of dementia research. The advent of innovative, sensitive diagnostic approaches is what most excites me in the field.”
I am personally hopeful for the future of dementia research. The advent of innovative, sensitive diagnostic approaches is what most excites me in the field. Currently, AD is incurable, a fact which has partly been attributed to its late diagnosis, when brain damage has already become widespread. Consequently, it is of crucial importance that an accurate diagnosis is given at an early stage, even before the appearance of symptoms. It is anticipated that any potential drug candidate will work more effectively in such cases. The use of artificial intelligence towards a rapid detection of subtle changes that might identify individuals who are destined to develop the disease in the future, is also a very promising area of research.
Finally, the development of efficient treatments is eagerly expected within the next decade. Preliminary results from ongoing clinical trials have shown some promise, with conclusive results from Phase II trials against amyloid-β currently being anticipated.
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neuro Central or Future Science Group.
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