Podcast – AAIC 2025 – Day Two

Voice Over:

The Dementia Researcher podcast, talking careers, research, conference highlights, and so much more.

Dr James Brady:

Hello and welcome to our ongoing podcast series, brought to you from the Alzheimer's Association International Conference from right here in sunny Toronto. I'm your host, Dr. James Brady. And it is my pleasure to bring to you today's episode, the second of four in a series designed to capture essentially the essence of AAIC 2025. Today I'm joined by three excellent guests. I have Dr. Lucy Stirland, an academic psychiatrist, I have Felix Wittmann, a PhD student from Leipzig University, and Isabel Castanho, a doctor who brings genomic expertise from Harvard Medical School. Each of them has packed a few solid days into AAIC 2025, but we're really here to find out what stood out for them the most. So before we get into the highlights, let's begin by hearing a little bit more from our guests with some proper introduction, including any sessions or posters they've been involved with here in Toronto. Isabel, would you like to start?

Dr Isabel Castanho:

Sure. Thank you, James. And thank you for the lovely introduction. It's my pleasure to be here and have this conversation with the other guests and with you. So as James said, I'm Isabel Castanho. I'm an instructor at BIDMC and Harvard Medical School in Boston. I'm a neurobiologist with a background in genomics of Alzheimer's disease. And in the past few years I've been studying deeply cognitive resilience or Alzheimer's disease resilience. And there what I'm interested in is in understanding the biology, so what's molecular and cellular biology happens in people that would have been classified as having Alzheimer's at autopsy but actually did not show any cognitive impairment when they were alive. And I find these individuals fascinating and so that's why I'm studying them, because I really believe that understanding what is happening in these people can help us design targets, really effective treatments for people that do develop a dementia. And so yesterday, Sunday morning, so I'm sorry it was not today, but I will mention it because it was a session that I presented, I presented my findings on molecular and cellular signatures of cognitive resilience. And the work that I shared yesterday is currently available as a preprint if anyone is interested in reading. And I'm very happy it was a great session. There was a lot of interest and it actually initiated a lot of conversations, corridor conversations with other people.

Dr James Brady:

Wonderful. I think that's one of the key things about AAIC 2025 or at least AAIC in general is those corridor conversations that you have with people, networking, meeting people, perhaps some new ideas as well.

Dr Isabel Castanho:

Absolutely, yeah.

Dr James Brady:

Have you found that with your experience across the conference or what have you seen?

Dr Lucy Stirland:

Yeah, I think being in person is brilliant, isn't it? I know I think they've said about 8,000 people are here in person and 3,000 online, which means it's really accessible for everyone. But being here in person means you can catch up with people and make new connections in a way that I really value being here.

Dr James Brady:

Awesome. So with your background, can you tell us a little bit about that and perhaps how that fits in with your interest in attending AAIC?

Dr Lucy Stirland:

Yeah, so as you mentioned, I'm an old age psychiatrist or geriatric psychiatrist depending on where you're from. And I work in Edinburgh in the UK. So I work about half in the health service in the NHS and about half in the University of Edinburgh. And my research interest is in comorbidity or multimorbidity, meaning people who have other chronic conditions alongside dementia. That's been my research interests about the last nine years since I started my PhD. And I think I talked about it last time I was on the podcast in 2019. Here we are still banging that drum. I had a poster yesterday, Sunday, which was presenting work that I did as a pilot project funded by the Global Brain Health Institute, who I am a senior Atlantic fellow with, having worked in San Francisco in 2022, '23. So they funded me to do a small piece of work with people with dementia and other conditions and carers of people with dementia and other conditions to take their research priorities, particular outcomes that they're interested in so that we can design research that focuses on the outcomes that are meaningful to people with dementia and other conditions and their carers.

So I have a poster of that. And like you said, mine's not preprint yet, but it's available on the GBHI website as a PDF if anyone wants to download the infographic. So that's the main research I presented. I've also hosted an immersive session on Friday, which was through our comorbidity and multimorbidity work group, which was a really, really stimulating session with people from lots of different backgrounds talking about research and different approaches to thinking about complicated people and how we might best manage and treat their dementia.

Dr James Brady:

Interesting. So if you had to pick one particular takeaway from your immersive, I mean it all sounds fascinating, what might it be? Was there anything that particularly stood out to you?

Dr Lucy Stirland:

Well, we were thinking particularly about consideration of comorbidity and multimorbidity in clinical trials. And I think the main thing for me to take away was that I think we always think about drug clinical trials, don't we? But actually clinical trials can be of multimodal interventions and prevention interventions and actually people with multiple conditions. It's the theme that's come through some of the sessions I've been to. You have to have a vascular risk factor to be eligible for a multimodal intervention. So it's relevant in the drug trials or even trials of biomarkers, which is another thing that's come up quite a bit, whether you have other conditions. But having another condition might mean you're more eligible for some of the other types of interventions. So that helped me really broaden what I thought about trial inclusion.

Dr James Brady:

Interesting. There's a lot to consider there. So speaking of considering things, Felix, how far through your PhD are you at the moment?

Felix Wittmann:

I'm actually in my second, third year, so I'm about to finish.

Dr James Brady:

Wow. And so is this your first AAIC?

Felix Wittmann:

It's my second AAIC. I've been there last year in Philadelphia as a first AAIC, so it's my second time. And still overwhelming, but also it's already a little bit used to it from first time, but super happy to be here.

Dr James Brady:

So in terms of things that are useful, what is it that you're studying? What's your thesis on?

Felix Wittmann:

Well, I have a background in sociology, but I'm working in the field of social medicine and epidemiology for some years now. And the last three years mostly or maybe kind of and exclusively in dementia, and I'm focusing on prevention risk reduction. The last years I was involved in the AgeWell study, which is a multi-domain lifestyle intervention study based on FINGER which we adopted in Germany. And I was mainly involved in the past or post-intervention period. And currently I'm focusing on maybe two more specific topics. The one which is what I also presented yesterday with the poster is to find some more specific risk groups for dementia based on the risk factors that are quite well known now from the Lancet Commission, et cetera, and to try to target intervention and prevention more specifically since we have those first very, very nice and big intervention studies like FINGER of course or AgeWell in Germany. And now we just heard the U.S. POINTER results today and they're quite impressive and the evidence is quite mixed yet and they're mostly have this one-size-fits-all approach. And then idea is to find more specific risk groups to target intervention more specifically. Yeah, that's what I'm actually doing. And another focuses on migration background and its role in this whole risk reduction prevention field.

Dr James Brady:

So do you think has your work so far and the things that you've been hearing around the conference, are there any one or two groups that you think have been largely overlooked or opportunities to intervene that seem to be clear?

Felix Wittmann:

Overlooked? What we found yet regarding those risk groups are especially two that are seem possible, like the ones with the cardiometabolic factors like with a high rate of heart disease, hypertension, diabetes, et cetera. The other one is mostly defined by social or behavioural factors like smoking, alcohol intake, lower physical activity, and maybe most it's the lower social participation. And we found one specific risk group, which was the smallest one with a high rate of obesity, which might be of interest. Yeah, interesting so far.

Dr James Brady:

So talking about risk factors, some of these are quite well known. Obviously there can be exposures early in life leading up to later life and potential outcomes obviously in later life. And so I guess let's start small at the cellular level. Isabel, you're looking at, your work concerns cellular resilience to threats. And so from any sessions today, has there been anything that's tickled you particularly? Is there anything that's stood out in terms of interest points around your area of expertise?

Dr Isabel Castanho:

So I'm going to apologise again because I'm going back a tiny bit to yesterday because yesterday was the resilience day. It was quite interesting. I wish I could say yes to your question from today. I understand in a way why it was one day. It was quite a long day focused on resilience. But actually sort of related, I do not work on the topics that you were just discussing, but that kind of mindset, those questions came up as we were discussing cognitive resilience even from a cellular perspective. So I mentioned my talk earlier that I gave yesterday, and that was actually part of a featured research session, FRS session that I submitted with my co-chair. So I co-chaired that session. So it was called Molecular Basis of Cognitive Resilience. And funny thing was that I had this idea, I pitched to my co-chair Tain last year at AAIC 2024.

We all had posters, Tain and I. So Tain Luquez is a PhD student at Columbia University. We had posters and someone else which we invited, Dr. Lauren Fish also had a poster. We realised we were all working in cognitive resilience and we thought let's join forces and submit a session. And so we then invited Gabriela Baldasso from Brazil to join us who was the youngest in our session. I was the most senior, believe it or not. And Gabriela just started her PhD. And then we also invited Susan Rohde from Amsterdam UMC, who's a PhD student. And let me tell you, so far that's my top highlight from AAIC because I was so proud at the end of that session. And all the feedback we got yesterday, everyone said that we really gave them a sense of bringing the community together. So all five of us, we are doing something that, well, we're all working in resilience, so there's an overlap there for sure. But rather than seeing each other as competitors, we're really trying to come together as a community.

And in that session, I'm looking more on a cellular perspective. Tain Luquez also is more on similar thing with different approaches, but also looking at single cell gene expression data. And then we had, but my results are pointing more towards neurons, his results also towards microglia. And then Gabriela brought a more astrocytic perspective. Susan told us about centenarians. And then Dr. Fish, Lauren is studying mice. So it was quite interesting to see how we were all coming in from different perspectives. And one of my highlights also of that session was the Q&A. So we left the last bit of the session was for questions and we actually couldn't cover everyone's questions because there were so many. But we got questions even from are you accounting for education, for lifestyle in these people? So we had such an interesting discussion around so many different things and even about the different methods. Why are the different speakers coming up with different cell types even? And we were all saying that it's more complementary than rather than a problem with limitations. It's more that it's just a complex problem that will have complex answers. But yeah, it was such, I'm leaving AAIC so proud of that session and motivated to continue my work. It was really, really interesting.

Dr James Brady:

Congratulations. I guess it seems to be increasingly the case that we've taken such a siloed approach I think in general within our own fields and we've seen some incredible advances within that, some really pointy, highly precise, highly targeted outcomes. But there's still a lot more work to do in terms of returning cognition if that can be, or protecting against decline to a greater extent. And it seems like that kind of collaboration, that sort of multi-field, multi-labelled, multi-layered approach, maybe that's the way forward.

Dr Isabel Castanho:

Absolutely.

Dr Lucy Stirland:

Can I ask, apart from the community building, which sounds brilliant, is there anything that excites you about cognitive resilience or anything that you think is going to be a target or something that we can apply clinically in future, something that's emerging? I'm sorry I missed your session.

Dr Isabel Castanho:

No.

Dr Lucy Stirland:

Give us the headline.

Dr Isabel Castanho:

This is the beauty of the virtual platform. You can actually go back and watch it if you miss it. So I'm going to be super biassed with my answer because that's what is exciting me right now with my own research, which I had my final slides was I tried to zoom in my take-home messages, and it's pointing me to the excitatory-inhibitory balance. So I really believe, and I gave a full disclosure at end of yesterday saying I did not start this work being a neurocentric person. We were actually expecting other things to come up and they did. But it seems like neurons are showing this main role in cognitive resilience from our data-driven approaches anyways. And I think it's still early and I'm hoping that in a few years there will be something that I can actually contribute to going to the clinic. But I think that it's something we need to go back into the old studies on hyperexcitability. Yeah, there's definitely something there that really excites me to move forward.

And then the other thing is also, which is again very complex, but is bringing all the different cell types, how are astrocytes, how the microglia, how are all of them contributing? And even there was someone asking me about how are the different brain regions communicating? And I was like, well, I love that question and I'm not an expert at all on that. I'm trying to zoom in into the cells. But I really hope that more people from imaging, from other neurophysiology topics help me understand also how my work fits into the broader picture of how different brain regions are communicating, which I think is also excites me a lot. Thank you for your question, Lucy.

Dr James Brady:

Lucy, it seems like working with the older adult population, cognitive research must be quite interesting to you. Is there anything that stood out to you particularly, I mean aside from unfortunately missing this fascinating session, is there anything that might change or has changed or influenced your thoughts about the current practise from AAIC 2025?

Dr Lucy Stirland:

I think it's been a great place to get the cutting edge science. So things like blood-based biomarkers and then the session yesterday morning, which is a bit beyond this podcast about lecanemab use. So I saw a great poster from Katheryn Cousins at the University of Pennsylvania. And she was looking at a relationship between creatinine, which is a marker of renal function, kidney impairment, and blood-based biomarkers for Alzheimer's dementia. And that's going to be really important when these blood-based biomarkers are used in the clinic more often is how we interpret the results from them. So she had 623 people in her sample and matched the biomarker sample results to electronic health records of a really diverse group of people. So it was people from different racial backgrounds, medically diverse, real world people. I think often these folk are tested, a lot of the samples we've seen and some of the presentations have been very educated volunteers, whereas this was real world people, matching their biomarker results to their electronic health records.

And she found that there are higher levels of creatinine, so this marker of renal impairment, kidney impairment were associated with higher levels of the tau and A-beta blood-based biomarkers, which is really relevant because lots of older adults will have kidney problems and how we then interpret the biomarkers based on that. Her suggestion would be that there might need to be an adjustment for creatinine. So when the lab's analysing the biomarker results, that they then can adjust for creatinine amongst that. Or something that goes in the clinical practise guidelines to say that when you're using these biomarkers, you need to account with these other things. And I saw another poster along the lines of biomarkers today. So I went to the lightning round presentation at 8:04 this morning. I just made it in time. And it was properly lightning. It was so quick that I nearly missed it.

There's an excellent researcher called Tamara Adrien from the University of Florida. And she had volunteers from their Alzheimer's dementia research centre in Florida. She had 512 people with and without dementia. And she was looking at increased blood pressure, so hypertension and type 2 diabetes separately and their relationships with biomarkers. And she found particularly there was a link with the GFAP biomarker, which I don't think is in line for clinical use in the UK at the moment certainly. But there's a link between high blood pressure and type 2 diabetes with higher levels of that biomarker in people with cognitive impairment. So that's going to be very interesting. She wants to look at that longitudinally to see if there's some kind of, if that tells us about how the biomarker might reflect what's causing cognitive impairment in those people. So it's very useful because it's kind of thinking is this about how we interpret the biomarkers, but it could also then feed back to what's the causal mechanisms behind all this. So that was really fascinating for me, particularly those two perspectives about biomarkers and other conditions.

Dr James Brady:

That's fascinating. So you're seeing with what Isabel's saying here, there needs to be maybe a combined effort of multiple different disciplines and approaches. With what you've found or with the sessions that you've heard, there needs to be additional factors considered to get a cleaner reading. It actually seems pretty promising that there's these new ways of using markers that perhaps I think creatinine's been around for quite a while now, but it seems like there's innovation in terms of how those sort of well-established markers are used to get a more and more accurate read of what's actually going on with physiology in the case of cognitive decline pathology. So Felix, I mean there's a lot that's been happening. It's a huge conference. So what's really been guiding your attention? What kind of things have been drawing you in?

Felix Wittmann:

I also attended one or two of the lecanemab sessions because I don't know that much about yet, but it was also quite complicated when you're not into this drug science and stuff. What I maybe like to mention since we just heard the final results of the U.S. Pointer study of course, which I guess is a highlight of this year's conference, which is or was a multi-domain lifestyle-based intervention study. They had two intervention groups, one group with a more structured intervention and the other one was a more self-guided. And they found effects on, positive effects on cognition within both groups, which is quite nice to see, quite impressive.

And I think I could link that to a poster which I just saw this morning from Jenni Lehtisalo from Finland was also quite involved in the FINGER study. And she did a meta-analysis of three randomised clinical trials. So with the FINGER study of course, then the J-MINT from Japan, the MAPT intervention study from France, and she analysed the effect of carrying the ApoA-IV and if this might have an effect on the effectiveness of multi-intervention studies. Indeed, there was this effect that ApoA-IV carriers have on the one side a higher risk for cognitive decline of course, but also showed greater benefits of this intervention studies, which is quite nice. And yeah, we see that this group of ApoA-IV carriers might be an important target group. And that matches both my specific interests for specific risk groups maybe. And then second might highlight those, the link of psychosocial social medical approaches, maybe a tool to the biomedical field. Yeah, these are two highlights so far.

Dr James Brady:

If you were to, back on the ApoA-IV, so if you were to consider trying to implement some of this knowledge into what you're currently doing, would you want any more information? Would you seek any other additional information to try and bridge that into what you're doing?

Felix Wittmann:

You mean when we would design or implement a new intervention study, for example?

Dr James Brady:

Yeah. What might that look like, that synthesis?

Felix Wittmann:

Of course it would be beneficial to have most information as possible, like having all the biomarkers and stuff so you know exactly what best to do. Maybe coming back to my own research, with having those risk groups, we have those factors which you can survey quite easy, more or less, maybe easier than big biomarkers or MRI data or something like that. And I think that could be a good approach to design intervention studies more specifically, maybe not like having a mixture between a one-size-fits-all study and a super individual based approach that you have certain risk groups. And that would be a great next step I guess.

Dr Lucy Stirland:

That ties in with a little bit with the session I went to this afternoon about, it was called Global Solutions for Dementia Prevention. And it was online sort of dementia training, psychoeducation, but also risk factor reduction sessions. And they made a really great point that if you can reduce risk at population level with something that's really low impact, like just an online training course, you could reduce, it might have a tiny effect size, but if you've got thousands of people doing that, that can reduce the prevalence of dementia significantly. And one of the studies, one of the Australian studies, there were several studies mentioned, but the Australian one was Maintain Your Brain by Henry Brodaty and University of New South Wales, Sydney. And he said that they might delay the onset dementia by a year in those people. And if you did that, that could reduce the prevalence of dementia by 10%.

Felix Wittmann:

Just by transferring knowledge.

Dr Lucy Stirland:

Exactly. Yeah, by using a low impact, relatively cheap intervention that could be accessible. I think the trouble is to then get educated people who want to do these things who do them. But it could be a really impactful way if equity was kind of embedded throughout the whole process.

Felix Wittmann:

That's a quite important topic in a broader sense, this effective communication of scientific insights on a broader level, like how can we transfer knowledge. And it was also mentioned by Katrin Seeher at the WHO Global Action Plan session this morning, who mentioned this transfer of knowledge as an important implementation strategy. And I just saw another poster, just to mention another short highlight because it matches perfect, by Niels Janssen from the Maastricht University. And they're actually running a small campaign, it's not that small, but they have four areas which differ in sociological factors. And they're running campaigns on a quite low budget level and incorporating with the football clubs and radio shows and having some advertising around. And they're measuring the knowledge of dementia and before and after within this 12 month. And they're not finished yet so there are no results yet, but quite interesting. And it's also something I've also always in mind, how can we transfer our knowledge on a broad level and make it have an impact in this case?

Dr James Brady:

It gets into that important factor about the troubles with cohort bias in some of these outreach initiatives. And one of the interesting things about that is perhaps for some groups, they would prefer to hear advice from friends rather than researchers or someone in a different position, I suppose. And so if there seems to be this hope in education disseminating information to reduce what sounds like a small amount with 10%, actually huge. Then perhaps finding ways to track those effects, map them, how they're spreading, who are the key players, there's potentially hope there. I mean these concepts are easy to grasp because they're very direct sort of human understanding in general. Isabel, how do you go about that translation to the general public with your work? Is there anyone who's done that particularly well that you've seen here?

Dr Isabel Castanho:

That's a great question. So I did my PhD in UK, in England, UK. And it was interesting. I did so much science communication then. And that's how I also got to collaborate with Dementia Researcher here on the podcast back when I was a PhD student. And it was such a blast. I think it's really a country... I don't know. I'm from Portugal, so I didn't see that at the level that I saw in the UK. The UK does such a good job with public engagement, intense communication. And when I moved to the States, I sort of found myself missing that because I wasn't seeing as much of that. That said, my first AAIC was here in Toronto nine years ago, and I've been seeing at the Alzheimer's Association actually shifting so much. Maybe they were doing that before, but maybe as a researcher I wasn't seeing that as much. And now I feel like they are doing such a great job actually bringing together more of the community and both communities, sorry, so the general community and the scientific community together. And now they have AAIC for all. That's so great to see.

And then on your conversation and your question actually, James, made me think about... Again, I'm sorry, this was yesterday. I promise I'll cover a highlight from today. But yesterday, Dr. Joanne Pike and Dr. Maria Carrillo from the Alzheimer's Association gave such inspiring speeches at the plenaries, really showing their leadership on an era where it's difficult right now to do science, funding is being questioned. And they, I think the Association is showing they are investing a lot on early career researchers like us. And they are speaking up, using their voice to go against this sort of attack on science that I feel on a daily basis. And then I went to the ask session they have where you can ask the plenary speakers questions. And I asked them, one of the questions that I asked them was, how can we help you and you help us with misinformation, which I think is something that is very related what we were just talking. And I see myself fighting that not as much with I do science communication as in outreach, but actually starting with family and friends even.

And so one thing that really stuck to me, and again will be one of my highlights from AAIC, was Dr. Carrillo's answer about integrity. That one, she thinks that a solution is for us researchers, us scientists, clinicians, to really show our integrity, be very open about our integrity because that will be the way to reestablish the trust from the public. And I thought, wow, yeah, that's really great just to show in our transparency, collaboration, being open, sometimes acknowledging limitations of our work or something that we maybe have overseen. And that integrity comment was brilliant. And then to try and come into a highlight from today. So now I'm going to shift gears if you're okay with that, James, because I am the basic scientist neurobiologist in the group. But this morning I went to a really exciting talk titled Crosstalk between Oligodendrocytes, Astrocytes, and Microglia. And two of the talks that I really enjoyed.

I'm a huge fan of Dr. Beth Stevens from Harvard. She does such beautiful work in looking at microglia. And she actually presented on interactions between microglia and synapses. So we know she's done a lot of work in this. There's others in the field that have shown how microglia engulfs, so eats up synapses. But she actually showed us data on how specific signals lead microglia to engulf specific synapses and not others. And I loved her slide that said to prune or not to prune, some synapses basically are engulfed and some are protected. And she's trying to understand why that happens, which microglia do what. And the idea is that further down the line, the idea would be to block the synapse pruning by microglia in order to recover cognitive impairment. And I thought that it was a brilliant talk. I highly recommend watching. And she's such a good communicator.

And then also in the same session, Dr. Eduardo Zimmer from Porto Alegre, Brazil, he focused a lot on astrocytes, how they're activated, the interaction, how they're involved in the interaction between A-beta and tau, and also the interaction between astrocytes and microglia. And on a not scientific necessarily take, but his last slide, I loved it. He had where he was showing his group and the people who worked with him, he had the title was Science is Made by People. And that actually brings me back to that integrity part and how at the end of the day, I think when I try to explain to my family when people start with conspiracy theories types of conversations, you know that it's people who are behind the science, who are behind these companies that you try to make as the evil of this world. Science is made of people. And I love that comment.

Dr James Brady:

It's interesting, isn't it, where there's this prevention or attempts to prevent pruning at the cellular level of being engulfed. Yet at the population level, we are trying to prune things, less sincere modes of communication within the population. So it's interesting.

Dr Isabel Castanho:

That's a great metaphor.

Dr James Brady:

It's an interesting contrast.

Dr Isabel Castanho:

It is.

Dr James Brady:

And so just before we finish up, I mean we've covered... And thank you so much for weaving these in so nicely. Zooming out, seems like there's a real focus on broadening interest areas, on collaborating between fields, and maintaining integrity while that's happening. As you're saying, in those plenary speaks, it was quite striking to see how powerful those speeches were. Really on the front foot, encouraging proactive lobbying of members for continued support for Alzheimer's disease and related dementias, which is of course why we're all here. And I think a record 600 travel fellowships work at this conference as well. So that's 600 researchers, young researchers who may not have otherwise been able to attend the conference. And in those cases where people may not have been able to attend, those virtual platforms, you're seeing a 61% share of women attending those hybrid platforms as well. So in terms of integrity, in terms of equity, it's really showing the importance of looking for those alternative solutions and seeking other methods to try and bring people in, which is hopefully what we'll achieve. If that can be done, then maybe there'll be more trust in the system and less scepticism perhaps around science, which is unfortunately what we seem to be seeing that's out there. Of course, we've had some quite powerful presentations at today's plenary event. So did anyone attend those? Is there anything?

Dr Lucy Stirland:

Yeah, I can talk about the first one. So this was by Katerina Akassoglou from the University of California, San Francisco Gladstone Institute. And the title was Neurovascular Interactions in Alzheimer's Disease from Mechanisms to Treatments. And as a clinician, I thought this was brilliantly executed because there was a lot of basic science, but it was very clear what the clinical application was going to be. So she was highlighting about blood proteins leaking into the brain, and particularly fibrin and fibrinogen, that their lab has studied in mice with fibrin knockouts. And then they've identified that as a mechanism for cerebral vascular pathology. And most importantly, they have an early phase trial linked to that lab with a fibrin-targeting monoclonal antibody, which looks like it could be really promising. So they've got phase one A and phase one B trials currently underway. So for me, that was a kind of exciting segue from the lab to potentially clinical in future.

Dr Isabel Castanho:

Yeah. I also really enjoyed the plenary. And I mentioned before both the talk from Dr. Beth Stevens from Harvard on microglia and my personal excitement on hyperexcitability. Like to answer your question, Lucy, it was quite interesting to hear how she's looking at or she's provided evidence on how microglia maintain network synchronisation and prevent hyperexcitability. So for me also coming out from the morning session on microglia and interaction with other cells, it was quite interesting to see that connection between biomarkers and then how it actually goes together with microglia. Then I also found the second plenary from Dr. Maria Grazia Spillantini from University of Cambridge, UK, that was quite interesting as well. The title was the Multiple Facets of Tau. And she walked us through the characterization of tau, including isoforms, mutations over the years in multiple tauopathies. And an example, I think my top highlight from that talk was how important it was to identify tau mutations in order to develop mouse and cell models to study tau and its progression in different tauopathies including Alzheimer's disease. Because we all know when families with mutations are studied, well, families with mutations both for Alzheimer's disease or frontal temporal dementia, you name it, they are rare, but can actually teach us a lot about the biology and help us make models where you can try to modulate what is happening in sporadic forms.

So it was quite interesting to see her explain or bring back decades of research on how it started with a simple mutation and now so many people are studying. And this I think brings us back to the importance of people joining studies. I don't have dementia, I hope I never get it, but I myself, for example, I've been involved in studies even looking through, I had a baby last year, so I-

Dr James Brady:

Congratulations.

Dr Isabel Castanho:

Thank you. And I actually was part of a study while I was pregnant. And this just to say that it's so valuable when people actually join studies, donate their brains or a blood sample because it can really lead, the small finding can change the field really. So yeah, so it was nice to see that actually coming together. It was a great session.

Dr James Brady:

It's a wonderful note to wrap up on actually is the benefits of contributing and of course not giving up on what might be considered niche areas. I guess you never know what the future of research holds in this respect. So on that, that brings us to the end of today's conversation. Huge thanks to Dr. Lucy Stirland, Felix Wittmann, and Isabel Castanho for taking the time out of a busy conference schedule to be here with us today. We will be back tomorrow with more reflections, insights, and stories from AAIC 2025. Until then, please subscribe wherever you get your podcasts. And don't forget to follow the Dementia Researcher community online. I'm Dr. James Brady, and thank you very much for listening.

Voice Over:

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