ISTAART Relay Podcast – Biofluid Based Biomarkers PIA

Voice Over:

Hello, and thank you for tuning into the third season of the ISTAART PIA Relay Podcast, brought to you by Dementia Researcher. ISTAART is a professional society and part of the Alzheimer’s Association, representing scientists, physicians, and other dementia professionals active in researching and understanding the causes and treatments of Alzheimer’s disease and other dementias. In this five-part series we’ve once again asked members of the ISTAART professional interest areas to take turns at interviewing their colleagues and being interviewed themselves, with the interviewee going on to be the interviewer of the next episode. We’ll be releasing one of these podcasts each day in the buildup to the Alzheimer’s Association International Conference to showcase the amazing work of the ISTAART PIAs. So, this week you’re going to hear all about fluid biomarkers, atypical Alzheimer’s disease, reserve, resilience, and protective factors, immunity and neurodegeneration, and technology and dementia with some amazing guests.

Erica Dove:

Hello everyone, and thanks for joining us. My name is Erica Dove, and I’m a PhD student from the University of Toronto in Canada, and also the communications student trainee for the technology and dementia professional interest area, also known as a PIA. Today, I’m delighted to be talking with Charlotte Teunissen. Hello, Charlotte, could you introduce yourself and tell us what PIA you’re involved with?

Professor Charlotte Teunissen:

Hello, Erica, and hello, all. My name is Charlotte Teunissen and I’m a professor in neurochemistry in Amsterdam University Medical Centers, and I’m the chair of the biofluids-based biomarkers PIA, so BBB PIA, as we call it.

Erica Dove:

Okay. Wow. Well, I come from the technology and dementia PIA, so I’m very interested because I don’t know anything about your PIA. I’d love to get a little bit to know you a little bit more, so could you tell us a little bit about your research and what brought you to dementia research?

Professor Charlotte Teunissen:

My research is aimed at developments of body fluid biomarkers for the use in patient’s care in neurological diseases, and our main focus is on dementia. So, not only Alzheimer’s dementia, but also other forms of dementia. We also do research into the use of body fluid biomarkers and implement them in multiple sclerosis. But the main focus is dementias, and in our research we want to follow the complete workflow or walk the complete roads of biomarker developments. So, from the identification, which we often do by proteomics methods, then we do validation, analytical developmental biomarker tests, that takes a lot of our time usually, and then analytical validation, clinical validation in the original groups and also in independence cohorts and also in different purposes. For example, you have a biomarker for Alzheimer’s, identifies for Alzheimer’s in a Alzheimer control study. Next, we want to know whether it’s also valid or specific for Alzheimer’s.

Professor Charlotte Teunissen:

So, absent in frontotemporal dementia or Lewy Body dementia and so forth and so forth, so longitudinal studies. And ultimately, we want to arrive at the clinical implementation, and we also have a large biobank here in Amsterdam, and that is a treasure box for our biomarker research, you can imagine, because at every step of the biomarker developments we need bio samples and we have them. So, that makes our life very easy also.

Professor Charlotte Teunissen:

And your second question was… Oh yeah, why did I enter the dementia research? Yeah, I’ve always, during my studies, I’ve been especially intrigued by the brain and how it works and different aspects like psychology, how do memories form, and so forth. How is behavior defines, but I’m also rather more a biologist, biochemist. So then, I encountered a PhD project in the Netherlands, biomarkers for dementia, and it was a perfect combination of my skills and it’s really attracted me. So, fortunately I got a job and that’s how I came to the dementia field. I’m still very happy to be part of it because it’s so intriguing. You have different aspects, behavior, social, and biological as well.

Erica Dove:

Absolutely, yeah. Looking at things really through that kind of bio-psychosocial model. I have a follow up question that’s actually related to your response to my first question, just because I do a lot of implementation research, so I wondered if you could talk a little bit more about biomarkers and when you were talking about clinical implementation, what does that look like?

Professor Charlotte Teunissen:

Clinical implementation of CSF biomarkers or blood-based biomarkers can mean that we use it really in clinical practice of memory clinics, for example, and that’s the first step and it’s easy or relatively easy for us because we have a very close connection. It’s just one-minute walk into the clinic and we have the infrastructure ready. So, that’s our play garden for novel tests, and we can do research also along with testing if the implementation works and how happy to physicians are, how much confidence they have in the results and if it affects their treatment decisions. But implementation also means, for example, that we develop apps to help in interpretation. For example, with neurofilament lights, it’s a axonal damage protein, and it can be used for many neurological disease to indicate that there is really ongoing axonal damage, but it’s also very much related to age.

Professor Charlotte Teunissen:

So, we developed an app with the reference ranges across ages so that people can use it and see where their patient’s results fits into the range of controls, or if it’s in the range of AD patients or in the range of FTD patients. So, that’s also part of implementation. And the second step beyond the academic implementation means that that we think ahead of implementation in peripheral hospitals, your third line through the second line, and maybe also through the first line, and that’s very exciting. There are many opportunities now with these biomarkers that may work, so there are also everyday new options for implementation, but one part of it is also reimbursements. And that’s also where I try to participate in studies because I think that we should be in the driving wheel, otherwise it won’t happen. So, it’s also our responsibility to make sure that people can use it and find a path to the reimbursement as well.

Erica Dove:

Mm-hmm. Especially, again, I’m no expert in your area, but I’m suspecting that for the type of research that you conduct, you probably need kind of a larger sample size, large numbers. Is that correct?

Professor Charlotte Teunissen:

That’s correct. Yeah. Maybe the [inaudible 00:08:03], yeah.

Erica Dove:

Yeah, so kind of the more the merrier, so if you can contribute, why not? Jumping back, you’ve said so many intriguing points that I really want to probe on further. One of the questions I have is, you mentioned apps and I wondered if you could describe how technology plays a role in your work and where you see technology going in the next five to 10 years in your work.

Professor Charlotte Teunissen:

And what do you mean with technology? Just the apps, IT technologies, or also all the technology?

Erica Dove:

All the technologies. Any way you define technology that you use in your work, like computer programs or anything like that.

Professor Charlotte Teunissen:

Yeah. So, the technologies are crucial for biofluid biomarker research. We really need technological… Or, we’re depending or take advantage of technologies that can measure at lower and lower concentrations. For example, with single molecule analysis or high-throughput analysis on automated platforms and also point-of-care technologies that must become increasingly specific. So, point of care, do you know what it is?

Erica Dove:

I’d love for you to tell the audience.

Professor Charlotte Teunissen:

Okay, yeah. So, point of care really means that you do the technology at, more or less, the bedside or at the place where you need the care. So, that goes with other requirements than analysis that you can do in large batches on a machine, where you usually have to have multiple samples analyzed at the same time to be cost effective, for example, but it takes a little bit longer before you have your results. And with point of care, you should measure it for one sample only, the technology should be less complicated but the results is then near the bedside very quickly, within 50 minutes or half an hour. But that’s not yet there, but it’s now being developed because the field of the blood-based biomarkers is accelerating. It has been very fantastic.

Professor Charlotte Teunissen:

We had fantastic results in the last years, so now it’s really, I feel that many parties are also interested in to help the development of novel tech measurement tools and so on. But with respect to IT and software possibilities, that becomes also very crucial for us, also because we do large population analysis. In our discovery studies, we measure multiple proteins, so the processing of the data becomes also more complicated. So, we need novel software tools or in our studio, for example, novel algorithms. But if you imagine that you need nine proteins for the optimal prediction of the disease progression, for example, and then you must be able to measure those nine proteins, but also you need some support to interpret it because it gets too complex at for… Yeah, if you have one protein and then it’s off the target or below the cutoff or a above the cutoff, and it’s easy to interpret, but if you have nine of them that it blows your mind. So, the technology really plays an important role in our research.

Erica Dove:

Yeah, it sounds like it, and it sounds like there’s a lot of advancements being made, which is very exciting. So, that leads me to my next question, which is kind of a good question with the Alzheimer’s Association International Conference coming up is, what are some of the hot topics in your field right now?

Professor Charlotte Teunissen:

You will be flooded by blood-based biomarkers in the Alzheimer’s disease. I think in the AAIC in San Diego as well. So, this is really a hot topic with very good biomarkers, especially the P-tau biomarkers. So, there is an issue whether… And there are several studies addressing it, and those will be presented, how early can we measure them? How sensitive are these? Is there advantage in measuring one P-tau, phospho-tau, isoform above the other? Or should we measure them all? Or maybe one is just the best, or maybe doesn’t make any difference. So, that’s really a hot topic and I expect multiple presentations around it.

Professor Charlotte Teunissen:

We are now also heavily discussing the implementation. So, probably there will be a presentation about appropriate use recommendations for those blood-based biomarkers. So, not only for P-tau, but also for the astroglia protein, GFAP, neurofilament lights that I mentioned already, and amyloids proteins as well. And that’s a paper that will come out shortly before the AAIC, and I think it will lead to a lot of discussion also, so it’s good to follow. Yeah. Oskar Hanson will be the first author on the paper and also the presenter, and I will be the last, so you can follow our names or search on our names in the program.

Erica Dove:

Congratulations on your publication.

Professor Charlotte Teunissen:

Thank you.

Erica Dove:

Those certainly sound like hot topics. So, I wonder with those hot topics… Actually, here’s more of a question of my ignorance. Can you use biomarkers to assess people for dementia?

Professor Charlotte Teunissen:

Nowadays, we can. Anyway, yeah, for using the CSF biomarkers, they are already implemented, but it’s not for dementia for the clinical syndrome but for the Alzheimer’s pathology, etiology of dementia. Yeah. That’s-

Erica Dove:

Okay. Sorry. I’m so curious. I come from clinical kind of background, so I wonder what would… I’m from Canada and the way the referral process works is different everywhere, but is somebody get screened with a pen and paper measure and then referred for a test? Or how does it work with the system in your area?

Professor Charlotte Teunissen:

Yeah. In the Netherlands, patients first goes to the primary care physician and then they do a pen and paper test nowadays. We are developing digital alternatives, but they are not yet implemented, and then if the primary care physician, they like to not refer as much as possible, not to overload the other lines in the care system. But once they have a suspicion that it’s really serious, of course, and enough indications then they’re referred to a memory clinic, and this can be a specialized memory clinic, which is usually in third lines or the academic medical hospitals or in the second line. There they can undergo a lumbar puncture or an amyloid PET scan, for example. But the lumbar puncture generates more information because you don’t have only amyloids information, but then you can also do analysis of P-tau and also of a neurofilament light, for example.

Professor Charlotte Teunissen:

So, in our memory clinic the lumbar puncture is preferred and that gives you an indication. It’s not in the first line that they do the lumbar punctures, but that’s done in second and the third line. Of course, in combination with the neuropsychological testing and the story of the patients, it’s not just doing a screening. But the future will probably go in a direction with those blood tests because they are so easy to perform and non-evasive that one can do a pre-screening using the blood test. And those who test really negative can be sent home and others that test positive and also in the gray zone, you can do additional testing, for example, by lumbar puncture and amyloid PETs. So, this is where it will go to in the end. How quickly? I don’t know. We hope very soon, but we must also do it very careful, not to give people… Send them home with the wrong answers.

Erica Dove:

Absolutely. Yeah, perfect. So, just looking at our time, I wonder now if we could switch a little bit over so I could learn a bit more about your PIA. Could you tell me a little bit about the fluid biomarkers PIA and how your group is organized?

Professor Charlotte Teunissen:

Yes, of course. So the BBB PIA, it’s quite a large PIA. I think it has over 600 members or even more now, I don’t know. We have 11 working groups, and those working groups, you can participate in it and they are working towards writing a paper together, or making some guidelines. Usually, one of the outputs of the working group is to author a paper, and they are also cross PIA. So, for example, we have a working group on the crossover… PIA collaboration with the FTD PIA, and we published the right paper or review last year or this year, even. Yeah. We also have imaging working group or with blood biomarkers in… No, body fluid biomarkers in Down syndrome or psychiatric disorders. Furthermore, we organize several webinars, and that’s the beauty of… Yeah, that’s why we’re now working more in Zoom.

Professor Charlotte Teunissen:

So, those webinars are very interesting because they’re well attended also, where we touch upon a specific subject. For example, the biomarkers in psychiatric disease or a health policy around biomarker use implementation. Since the field is accelerating, there is also more demands, or also by the members of the PIA to organize such webinars. We have a journal club and there are two young people interview authors of two different papers that’s also very interesting. We have a year in review online seminar, what happens in the past year, what are really exciting developments, and there are a couple of features research sessions, also, as AAIC. So, about the implementation, the other is neuroinflammation and BBB PIA FRS.

Professor Charlotte Teunissen:

So, at least two, and there’s also a symposium dedicated to the biomarkers. It’s called The Road Towards Clinical Implementation, so the subject that we just discussed. There are a lot of activities and we have executive board meetings, I think four times a year.

Erica Dove:

Wow. Yeah. It certainly sounds like a very active PIA and a really big membership, so congratulations on that. I wondered if you would know what your membership consisted of in terms of disciplines. Is it very multidisciplinary or is it more people coming from the same area?

Professor Charlotte Teunissen:

No, I think it’s very much multidisciplinary. Yeah. From different… There are lots of doctors, of course, but also biochemists. That’s more the audience of the AAIC, I think.

Erica Dove:

Okay.

Professor Charlotte Teunissen:

Yeah.

Erica Dove:

And then, how does the work of your PIA support your field of research?

Professor Charlotte Teunissen:

Yeah, it’s really helpful. For example, we also have a working group studying the pre analytics and that leads to an SOP, so standards operating procedure. So, recommendations also for how to process your blood samples when you obtain them from the patients. We made recommendations for that, and currently we want to refine them. The PIA is also helping to connect people through the webinars, and also on the PIA day. It’s really a platform to encounter each other, inspire each other, and we also appreciate the inputs of the young people. So, the early career researchers and they can send in their abstracts at AAIC, and if they indicate whether they want to be participate in our PIA sessions, then they can be selected also for our PIA date to give a short presentation. So, we welcome the exchange and, really, the inputs of young researchers is very much valued.

Erica Dove:

Ah, that’s perfect. That leads me to my next question, which is how can listeners, such as early career researchers, become involved in your PIA?

Professor Charlotte Teunissen:

First, you can indicate it… the tick books, the checkbooks in the membership of the ISTAART, you can indicate that here are in the PIA because want to be member of it, because then you are a member and you receive all the mailings and announcements of all the activities and then be at activities. But also, you can indicate whether you want to send me an email, for example, or via Jodi of the ISTAART, that you want to participate in an online seminar, for example, or a journal club. Especially journal clubs should be driven or hosted by the young researchers, so it’s interesting to hear of people who want to do that. So, you can become an active member right from the start.

Erica Dove:

Yeah, and I think what’s so interesting is, because your PIA, kind of like mine, is so multidisciplinary, everyone brings a unique lens that’s advantageous in some way. Everyone brings something to the table, so even if you’ve never been involved in this kind of research, early career researcher, it’s still good to get your feet wet. So, we are running out of time for today’s podcast recording, but before we go, I do have one final question for you which kind of leads off of our conversation, which is, what advice would you give to an aspiring early career researcher out there who’s thinking of looking into dementia?

Professor Charlotte Teunissen:

Maybe try to find a good spot where you can do your research, and a good spot means somewhere where you like the people, and where you get excited about the project, and where you can learn something new, because I think you may think ahead of your career path strategically, but I think you never know how it goes. And most important is to do what you like the most yourself and what inspires you, because then you will become the best in your subject. If it’s a very specific question how to make that next step, now, be aware every researcher likes to talk about their research, so you can just approach someone at the conferences, show them your interest, show them that you are really [inaudible 00:25:16] of approaching that specific person that you are interested in the work of the person and that you have ideas about the research fields, or maybe just go there and show your interest.

Professor Charlotte Teunissen:

You don’t have to have a defined plan, of course, but if you are enthusiastic researcher and after that, ask the email address and then approach that person afterwards after AAIC, because then you show that you are really committed and that will help, and then hopefully, they have a position for you.

Erica Dove:

That’s such tangible and practical advice. Thank you so much. I really appreciate that, and I’m sure our listeners do as well. So, that is all we have for our podcast today. Thank you again to Charlotte for taking the time to join us today.

Professor Charlotte Teunissen:

Yeah. Thank you, Erica for the fantastic interview you did. Nice questions. Thank you.

Voice Over:

Thank you for listening over the last week. ISTAART professional interest areas are a great way to expand your network and find new collaborators, and we hope these podcasts have inspired you to become involved. There really is a PIA for everybody working in all areas of discovery, and even better, ISTAART membership is now free for students worldwide and everybody of all grids living and working in lower and middle-income countries. You’ll find profiles on today’s panelists and information on how to become involved in ISTAART on our website at dementiaresearcher.nihr.ac.uk and also at als.org/ISTAART. There’ll be a link in the show notes. We’re looking forward to next week’s AAIC conference in San Diego, so if you haven’t already registered, visit als.org for more information, and it’s free for anybody who’s an ISTAART member and attending online. Finally, please do like and subscribe this podcast in all your podcast apps, and remember, you’ll find a video version exclusively on our YouTube channel. Thank you for listening, and we’ll be back in two weeks time.

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