Podcast – AAIC 2026 – Day Three

Voiceover:

The "Dementia Researcher Podcast," talking careers and research, sharing conference highlights, and so much more.

Adam Smith:

Hello, and welcome to the "Dementia Researcher Podcast." I'm Adam Smith, and this is the third of our daily highlight shows from the Alzheimer's Association International Conference, or AAIC 2026, taking place in London and online. It's day three, and the conference programme is still moving at full speed. There are major sessions, rapid presentations, posters, and conversations, all competing for attention, and every attendee follows a slightly different route through it, and that's why we hope these daily catchups are useful so we can compare notes and bring more of the conference into view. Joining me to look back on the third day are Cari Randa-Beaulieu, who is a provincial coordinator and knowledge mobilisation expert at the Alzheimer Society of British Columbia and Yukon, and Abrar AbuHamdia, who is a PhD candidate at Hamad Bin Khalifa University in Qatar. Hi. Both of you, thank you very much for joining.

Cari Randa-Beaulieu:

Hello. So happy to be here.

Abrar AbuHamdia:

Thank you.

Adam Smith:

So, to begin, let's put some voices and research interests behind those introductions. Please could you tell me a little bit about yourself, where you work or study, and some of the research that you do? Cari, I'll come to you first.

Cari Randa-Beaulieu:

Absolutely, so, I started out with a Bachelor of Arts in Psychology and minored in early learning. And somehow, I ended up at the opposite end of the life course, really focusing on dementia and end-of-life care, so I worked in long-term care for several years, where I tailored my art therapy practise through cognitive and physical accessibility adaptations. And during the pandemic, I had the brilliant idea to go back for a master's in gerontology, because there wasn't enough going on in the world at that time, and that's how I really got introduced to knowledge mobilisation as well as community-engaged dementia-focused research. And over time, accessibility, inclusion, and meaningful engagement is really core to my work.

So, at the Alzheimer Society of British Columbia and Yukon we seek to change the future for people affected by dementia by championing dementia-inclusive research, investing in innovative research, and acting as a knowledge source and fostering relationships with researchers and the community, so we really want people living with dementia and caregivers to know about the abundant opportunities to engage in research, not just as research participants but also as advisors, consultants, and partners.

Adam Smith:

It makes it so much more rewarding, doesn't it, when you've got a direct line of sight between what you do and the kind of people you're trying to support? And I love all the movement we've had over the last couple of years to make sure that co-design, which I know is a bit of a buzzword right now but is at the heart of what you do. I am going to ask question about your deciding to do that during the pandemic, though. Does that mean that you studied during the pandemic, too? Was that.

Cari Randa-Beaulieu:

Yes, I did, and that is part of what motivated my move from direct care to working in research. Because I had never worked in research before, I was really one of those undergraduate students who was like, "I'm going to volunteer, and I know I want to work in long-term care," and I never really saw research as a place for me. And throughout my graduate training, my supervisor presented me with the opportunity to work as a research project manager on a large, multisite interinstitutional dementia strategic-funded research project in Canada, called DemSCAPE, which looked at supportive features of the neighbourhood-built environment to support people living with dementia to age in place, in their communities. And it just really opened up a whole new world and career path for me.

Adam Smith:

That's brilliant, and I do think we need. We still need more research into those kind of arts and spaces because without that research it's still so hard to persuade policymakers and funders that that is a good investment, and I think the research that provides the evidence base for that and to show that it's cost-effective and welcomed is only. It's only by doing that that we're actually going to see more of those services that we know people value so much, so well done, thank you very much, Cari. And I'll come to you now, Abrar.

Abrar AbuHamdia:

I'm a PhD candidate in biopsychology and neuroscience at Hamad Bin Khalifa University. I'm also an ISTAART and a member of ISTAART's professional interest area Comorbidity and Multimorbidity in Dementia. I work for several years on patient case studies, which shaped my interest in neurological diseases. More recently, I transitioned into basic research as now I'm interested to learn about the mechanism of the diseases, learning about molecular, genetic, and cellular level, which led me to basic neuroscience research, where during my master's degree I develop a protocol for generating brain organoids with native microglia. And I'm now excited to build on this foundation by using these models to study neurological diseases. So, I think this combination shapes me as a person who is scientifically curious about the brain but always thinking about the patient at the other end of our research.

Adam Smith:

Yeah. That's great. And how are you finding being a member of ISTAART, 'cause it's a great kind of doorway into that wider community, isn't it? And being an ambassador, as well, is really exciting. I'm surprised you're not there in person.

Abrar AbuHamdia:

Actually, I joined ISTAART two years ago, and I attended AAIC 2012 in Philadelphia. It was my first time going abroad alone. And after that, actually, I pursued a master's degree in genomic and precision medicine, and I did this research in brain organoids.

Adam Smith:

Fantastic. Well, thank you so much, both of you, for being here. We did have a third guest, but unfortunately, we've had a few technical issues, so they've not been able to join us; however, I do feel that we've probably attended a lot of sessions between us today, so we're going to bring you all the highlights from day three. So now I'm going to ask Cari and Abrar to open their virtual notebooks and think back across the day, and I'm going to come to you, Cari, first for your first highlight of the day. What have you seen today that you most want to tell us about?

Cari Randa-Beaulieu:

Surprise, surprise. The social sciences qualitative researcher is really going to focus on the qualitative side of AAIC. So, the first session that really stood out to me was "Family and Social Impact of Dementia: Caregiving Work and Policy." And in summary, these presentations went deep into data, showing how caregiving for someone living with dementia impacts quality of life, economic stability, as well as sense of self. So, data tells the story of why supportive policies and workplaces matter for people in the sandwich generation. So, those are people around midlife who may have young children or are part of a community of care, which also includes either ageing parents or other older adults in their lives. And this especially affects women who face considerable long-term earning loss. The economic data is pretty sobering, making it compelling and clear that it's not just income.

Reduced long-term earning and the challenges of juggling multiple roles during peak earning years influences many other facets of quality of life. The presentation that really stood out to me within this session was presented by Lycia Tramujas Vasconcellos Neumann, "Elevating Caregivers' Voices: The Lived Impacts on Caregivers along the Dementia Journey." This really resonated for me. So, lived experience voices inform everything we do at the Alzheimer Society of British Columbia and Yukon, from our resource development to advocacy, education development, and, of course, research. We engage people living with dementia, but we also include caregivers or care partners or carers, depending on which country you're joining us from, as people with lived experience of dementia. So, what's behind the numbers? It's people.

To be truly person-centred, lived experience panel reviews, focus groups, lived experience collaborators in research and so many other facets are essential throughout every phase of a research project or initiative. That's why our team at the Alzheimer Society of British Columbia and Yukon, in collaboration with Emily Carr University's Health Design Lab and the University of Victoria, created "Collaborative Minds," a guide to meaningfully engaging people with lived experience of dementia in biomedical research. You can view our virtual poster, number 9355, in the digital portal and head to alzbc.org/collabminds to download the researcher guide, lived experience handbook, reflection questions, and practical tools and resources.

This resource actually builds off a guide for qualitative researchers called "Collaborate Gather Share." And we've heard from lived experience partners that participating in research through sustained long-term engagements also bolster their confidence as participants in society and, like, maintaining a meaningful life as well as the honoraria can supplement their income if facing early retirement as well as the cost of care and planning for the future.

Adam Smith:

What were the big takeaways from that particular presentation?

Cari Randa-Beaulieu:

Well, like I said, the economic side presents really concrete data for something that can be brought to policymakers, like, "This is why supportive workplaces and broader policies matter, to help caregivers stay in the workforce in a way that can sustain their quality of life."

Adam Smith:

So, they were making the economic argument that we needed to change jobs to enable people to take on that caring responsibility.

Cari Randa-Beaulieu:

Yeah, without being sort of financially squeezed out of the workforce to be either full-time caregivers or having to make really difficult choices.

Adam Smith:

Yeah, and that's difficult, isn't it, 'cause no two health systems across the world seem to be the same when it comes to this? Some are better than others at supporting that unpaid carer, although I don't think. I'm pretty sure I don't think anywhere in the world is really great at that. I think certainly where there's that more cultural element of people caring for older people, whether they do or don't have dementia, where older people go to live with family members and things, maybe in society it's slightly better there but also, as well, more likely to be a hidden issue, were.

Cari Randa-Beaulieu:

Yeah, and a fairly new facet of benefits programmes and, like, workplace benefit systems, having flexible sick time. It's not just illness. It includes paid time off or secured time off to support with doctor's visits or any sort of caregiving needs that would pull someone out of work for a chunk of the day.

Adam Smith:

Yeah. Thank you very much. Abrar, I'm going to come to you for your first highlight now.

Abrar AbuHamdia:

Yeah, for me, it is a session that's titled "Developing Topics in Factors Affecting Fluid Biomarkers." For me, this was very interested to me because I did my bachelor's degree in medical laboratory science and I also work in clinical lab. And we often were thinking about pre-analytical variables: fasting status, timing of sample collection, medication, sample handling, and assay interference. And now as, you know, biomarkers are becoming more central in neurodegenerative diseases and have high potential in making diagnosis more accessible, less invasive, and potentially earlier, I sincerely appreciated that in this session the speakers ask, "Can this.” Like, instead of asking, "Can this biomarker detect Alzheimer's disease pathology?" they asked, "When might this biomarker mislead us?" And the part I found especially interesting was by Dr Hanna Huber, who discussed the effects of food intake on plasma phosphorylated tau-217.

In this study, participants fasted for 12 hours. And then they had a sample collection, blood sample. After that, they had a meal and a follow-up, another blood-sample collection after three hours. And according to the presentation, she found that phosphorylated tau-217 level change after a meal in both healthy and Alzheimer's disease patients, and it showed that among 36 individuals with subjective cognitive decline or mild cognitive impairment who were non-fasting, 24 patients should have had an altered probability category if they had been fasting. More specifically, 11% individuals tested from low probability category to an intermediate probability category and 13% tested from an intermediate probability category to a high probability category. And as you see here, it's really critical because, like, it leads to different clinical decisions.

And I see that, as Alzheimer biomarkers become more widely used, it becomes very necessary to develop clear and standardised protocols for these biomarkers. Otherwise, we may end up building diagnosis and treatment on misleading results. There was also a question from the audience that I really liked. She asked whether food-related changes in plasma phosphorylated tau-217 could reflect a biological mechanism, and she mentioned the contribution of the autonomic nervous system. I found this question very interesting because it shifted the discussion from simply asking whether the meal interferes with the measurement — for example, through assay performance, antigen-antibody interaction, or changes in the plasma matrix — to asking whether food intake may actually trigger physiological changes that alter the biomarker level itself.

Adam Smith:

Do you know what? I think you're the first person I've heard talk, or that's the first time I've heard anybody talk, about the conditions under which the blood tests were taken, but it seems obvious when you say it. There are lots of tests where you're asked to do this fasted, aren't you? If you go for a cholesterol test, they prefer you to, you know, do that after you've fasted. It makes sense that they do this, so getting the guidance right to say, "Hey, you know, you need to do this consistently," that they should maybe run that test, not just, as you say, just rely upon one test, but actually you should do multiples over a week and average this out and take them at different times of day, perhaps. I don't know. I'd be interested to have a biomarker. I should contact. Amanda Heslegrave, if you're listening to this right now, message me, and tell me.

Talk to me more about this 'cause it feels like we could do a whole separate podcast on that topic. Thank you so much. That was great. So, that's our first. I'm going to add in a highlight of my own, and hopefully, I'm not going to steal one of your highlights. I'm going to bring up Dr Betty Tijms' talk. This is one of the plenaries. Betty has been on the podcast before, one of our "Relay" shows quite a few years ago now and is from the Amsterdam UMC. And she gave a great talk that challenged the assumption that Alzheimer's disease is a single disease. And her team have used CSF to identify at least what they think are five separate biological subtypes of Alzheimer's disease with very distinct molecular mechanisms in the genetics and progression rates as well.

And she showed evidence that these subtypes appear early, even before cognitive symptoms, and may explain why different drug trials fail and also kind of making the point that treatments aimed at one pathway alone might only work in one specific subtype, which brings back this thing that was talked about on the podcast yesterday, and it's been talked about lots, which is this idea of precision medicine and tailoring therapies to patients' very specific molecular subtypes rather than saying, "This is for Alzheimer's alone." Yeah, anybody who's listening should definitely go and watch her presentation 'cause she gave some great slides where she showed on the screen where you got really into the epigenetics and looking at this, where you have these little clusters to go, "That is these people. That is these." And there was the very distinct thing that these were different types.

And so, you couldn't expect that one treatment would work on all of them, 'cause they all were very different. So, three key takeaways were that Alzheimer's is likely not a single disease; that heterogeneity may explain past trial failures as well, why it was working not in the whole cohorts; and precision medicine needs to become a realistic goal for addressing that. So that was a great talk. So, we're going to come round for our next round-the-table. A conference highlight doesn't always have to be one of the big headlines or one of the big plenaries, of course. So, what did you encounter today? Was there a new idea or something new or challenged an assumption? I'll come to you first this time around, Abrar.

Abrar AbuHamdia:

The next talk that really stuck with me was by Dr Marco Colonna, who discussed a very innovative CAR-based therapy approach. I am very interested in CAR therapy, which is usually used in cancer to target and kill cancer cells. In neurology, though, it is different. Here, the idea was built around designing an anti-amyloid chimeric antigen receptor that could be expressed in astrocytes and activate phagocytosis-related pathways. He reported that these CAR astrocytes reduced amyloid-associated pathology after plaques had already formed and also prevented early plaque deposition in vivo. In addition, they prevented microglial exhaustion. That was really interesting because astrocytes do not normally have that function; they are not phagocytic cells.

It's a function of microglia, and because it's more abundant than microglia, they modulate the cells, like, to help microglia. I just like, like, the way because they thought different about therapy. I know this treatment is really early and preclinical and there are safe and delivery questions to solve, but conceptually, it opens a very interesting direction for neurodegenerative diseases treatment.

Adam Smith:

Absolutely. I feel like microglia was something we were talking, like, nonstop. It was, like, the whole theme of AAIC maybe three-four years ago. I'm sure it is now if you're picking out those sessions. So, it had an interesting delivery mechanism as well.

Abrar AbuHamdia:

Yes, and they actually use it now for multiple sclerosis.

Adam Smith:

Fantastic. Thank you very much. And Cari, I'll come to you for your next highlight now.

Cari Randa-Beaulieu:

Yeah, thanks for the probe about challenging assumptions. I sometimes feel like I'm so focused on living well with dementia that I kind of forget about the role of general brain health, so my next session of interest was "Brain Health in Action: Organization-Led Efforts across the Globe." So, this session highlighted how organisations from the UK, Latin America, Australia, and the US are leveraging evidence to develop policies, programmes, and initiatives that promote and advance brain health across the life course. From the randomised controlled FINGER to POINTER and now the Latin American FINGERS trial, the presenters made it clear that there's no singular silver bullet intervention for brain health.

Individual preferences and social determinants of health, cultural diversity, and regional infrastructure influenced the growing need to translate findings into real-world action to drive public health and public policy efforts to really zoom in on brain health for more of a preventative approach. Matthew Baumgart from the Alzheimer's Association really summed up the themes across all presentations in this session so well. He closed with "scientific findings are the starting point, not the finish line." Across all presentations from global researchers, I heard the importance of going to communities and centering interventions in the priorities of specific communities for maximum uptake and benefit. Especially from Ross Dunne in "From Prototype to Platform: Scaling a Brain Health Clinic.” He spoke to the role of stigma around where a clinic is located.

To have an MRI machine on-site, the clinic was located in a mental health services building, which was incredibly unappealing to Manchester's large South Asian population, which is very similar to the population in Metro Vancouver. So, the choice of naming it a brain health clinic made it more appealing. And it can sound trite, but words really do matter. When we think about stigma, there are words and concepts that don't translate or reinforce negative connotations, so community consultation and collaboration ultimately help build more meaningful resources and services.

Adam Smith:

Yeah, I agree. I think I've often. So, if in the UK. Obviously, I'm from the UK, and I'm actually familiar with this memory clinic, well, this brain health clinic, in Manchester. In the UK, the traditional route you might see or that most people go through when they present with a memory problem is through primary care and then to a mental health service and a consultant old-age psychiatrist. And they are referred to psychiatry. Only a much smaller number of people will go to see a neurologist if they're presenting with one of the potentially rarer forms of dementia, you know, FTD or maybe Lewy body or one of those other dementias. And that is a problem because people are concerned. They don't want to be. They think of psychiatrists as being somebody you see if you're mentally unwell, and they don't feel, you know, mentally well. They think that there's something wrong with their brain. It's not.

They don't associate that kind of same mental problem with a physical issue, so it's been a long-standing issue, I think, whereas in the US, of course, nearly everybody will see a neurologist. They work in different spaces, and I think that's a difficulty across the world. I don't know though. Do you. I am increasingly of the opinion; I don't know if you'd agree, both of you; that we now rapidly reaching a point where we know what good brain health looks like. The gap is doing something with all that information, like taking all that we've learnt from the "Lancet" report. I'm not saying that we don't know what causes dementia, but we know what kind of things you can do, the things that you need to do to potentially avoid it. And I'm not saying that we know everything. Clearly, there’s.

You know, there's always more we can learn, but I think what we're seeing now is there's shift to lots of research which is testing out how we deliver what we know about brain health to different populations of people in different parts of the world and then what the impact of that is, like we've talked about, FINGERS trial, and we've talked about the POINTER study, which is all about taking information we already have and seeing if we can make that to make that sea change that we

Cari Randa-Beaulieu:

And Ross Dunne did mention that motivational interviewing is a large part of how their clinic interfaces with the public. And I think that that sort of strengths-based approach. We also know that's a really great way to ensure buy-in is "hey, you have so much agency, and you have so much power, and there's things that you can do today to make a difference."

Adam Smith:

Absolutely. I'm going to jump off the back here and pick up on one of my next. I'm going to pick on a. I've got a poster here. So, we did a podcast a little while ago on what it's like to be a researcher living with ADHD. So, I was kind of interested to. I just did the keyword search to see if anybody was looking at ADHD. And there was. I found one poster, which was called "Neuropsychological Profile of Adults with a History of ADHD in the Absence of a Neurocognitive Disorder." This was Waleska Berrios, who's from Buenos Aires in Argentina, and this poster looked at adults under 60 who'd reported a cognitive concern but did not meet the criteria for having a neurocognitive disorder, because we’re. I know that ADHD is now more.

The symptoms of it are more widely acknowledged, and it's being diagnosed more, but you feel like the people who are developing dementia now would probably be unlikely to have ever gone through that ADHD-diagnosis process but might actually have it. And I'm interested to see how that might be impacting, you know, the dementia that they might be developing now. And these researchers compared people with and without probable history of childhood ADHD and found that the ADHD group had poorer verbal memory, slower processing speed, even after accounting for demographic factors and depressive symptoms, and they also reported that more symptoms of depression were independently affected performance. So, if you had ADHD when you were younger, if I'm reading this poster correctly, you were going to have worse symptoms if you got dementia later.

And I like this poster 'cause it reminds us, if you like, that poor cognitive tests in older life can be based on lots of other things, not just that you've got dementia. You're testing everything else in that moment. You know, in that moment that you're doing the test, there could be so much more going on, but because they're there as suspected dementia, they don't necessarily look more holistically at everything that's going on. And we might have this group of people that have lived with ADHD, but they probably won't ask them those questions. But if you've been always disorganised and then suddenly you get older and you're more disorganised, it might not be that they say, "Oh, well, that's 'cause you had ADHD before it," so. I don't know. So, there's an interesting connection. And I think there's a lot more opportunity to look at older people who might have ADHD to see what that might be doing about their life in dementia.

So, let's come back again. I've got. I think I've still got two more posters and one talk to talk to, so I'm going to come back to you, Cari, this time. Let's get your next highlight.

Cari Randa-Beaulieu:

Absolutely. Surprise, surprise, the art therapist wants to talk about improving brain health and dementia care through art and technology. This session was chaired by Deanna Willis and Frank Lai. So, it's not just my bias as an art therapist talking. Creative expression is central to the human experience. Embodied movement, theatrical performance, experiential learning in virtual reality, building children's empathy for intergenerational families affected by dementia, these presentations highlighted the marriage of old and new ways of storytelling and sharing lived experience. So, I really want to focus on "Empathy Through Animation: Supporting Moral Development in Children of Dementia-Affected Families," presented by Frank Lai. So, in this presentation, it was really hit home that animation-based storytelling is a powerful psychosocial tool for promoting empathy and moral development in children impacted by dementia caregiving.

This small-scale study was an exciting step to set the foundation for more cultural tailoring of the animations and potential integration into family-centred dementia-care programmes to strengthen resilience in caregiving households. So, I know at our organisation we're really seeing a hunger for more intergenerational supports, looking at younger caregivers especially as we have more people being diagnosed with younger-onset dementia. It may be a younger adult supporting a parent or intergenerational households, where youth have been left out of dementia support conversations. So, I'm noticing in my own work but also in these sessions this shift in focus towards bringing in bigger family structures and opening up who is supporting a person living with dementia. So, what I found particularly interesting or even sort of, like.

If Frank Lai and that team happens to see this, I would encourage future iterations of the animation to be developed through a co-design approach. The downside of attending a conference virtually is you miss out on those opportunities to ask questions in the moment. So, in my experience and just sort of as an observer, it wasn't covered how the animations were produced, and I think co-design is such a great way to sort of walk the walk of nothing about us without us. Our collaborators at Emily Carr University's Health Design Lab, in a previous project, partnered with BC Mental Health and Substance Use Services for a series of stigma-reduction animated shorts, where staff who had intersectional identities as service and care providers but also with mental-health-related lived experiences partnered with animation and design students.

And they were able to create these shorts where there was sort of visual representations of some really challenging themes, but they're transformed through visual metaphors, and they create just enough abstraction to also protect the person's identity. While this example doesn't have a dementia focus, the co-design approach is totally applicable and further supports the high-level goal of intergenerational communities of support around people affected by dementia. And oftentimes, in these co-design projects. And I speak from my lived experience too that in working with people with lived experience in these sustained co-design projects you create and nurture really fulfilling relationships. Those relationships are where you get sort of the hard truths when trust is built.

A person with lived experience will tell you how they really feel about something, and it amazingly shapes the research process for, like, "oh, I, as a researcher, have lots of biases and assumptions about the way methods need to be carried out" and for someone living with dementia to have the confidence and trust to say, "Ooh, I would not do it this way," and "This is how I would do it," shapes for much-more-meaningful respectful collaborative research.

Adam Smith:

Yeah, I completely agree, and what I really like as well is that that research has even been presented at AAIC, 'cause it's not that many years ago you would never have seen a poster like that at AAIC. And I love the idea that that's pinned up on a board in a poster hall somewhere now where we've got fundamental scientists and other people to kind of try and improve everybody's awareness of the different things that are going on across the research spectrum so we can all learn a little bit so that though researchers that can do that can learn a bit more about the biology and the biologists can come and learn a little bit more about what it means to do co-design, 'cause fundamentally. I know your poster talks to this, but there isn't a lot of co-design or patient or public involvement in that fundamental-science space.

Cari Randa-Beaulieu:

One of my favourite quotes from a lived experience partner has been, "I want to learn about rat brains!" So, the interest is there.

Adam Smith:

Yeah, I completely agree, and just a plug, we did a podcast a few months ago. There's a great piece of work going on with Hannah Gardner and Patricia Masterson-Algar, and they're from Dementia UK and Bangor University, who've got a new piece of research that just got funded looking at the impact on teenage carers and what it means to them and how they can create communities to support teenage carers and how they go through this when their families develop. We did a great podcast on that a few months ago now, so do look that.

Cari Randa-Beaulieu:

Amazing, I'll have to check that out.

Adam Smith:

I'm going to give you a minute, Abrar, but I'm going to do one of mine first. I've got two here, and this is a plug for UCL study 'cause I work at UCL. This is called; we can't get through a podcast without mentioning AI at least once; "Explainable Artificial Intelligence for Automated Amyloid-PET Positivity Classification," and this is as you would. The title is very descriptive. So, this is Sophie Martin at UCL, and this study explores whether AI could accurately classify amyloid PET scans while also explaining why it reached the decision it did so not just, you know, "that one has amyloid. That one doesn't" but explaining why it came to that decision. And the team trained a deep learning model on 1,300 brain scans from AMYPAD, achieving an overall test accuracy of 93%.

What I really liked about this is that the researchers weren't just satisfied with simply building a correct algorithm, but they also wanted it to explain why, as well, you know, so that it helps build trust between clinicians and the AI. So, the AI could say, "This one is positive, and here's why I think so." That's going to make a big difference when you're starting to ask clinical people to trust AI algorithms if it can explain its decision-making in with the process, so I really liked that poster. And yeah, that's Sophie Martin, UCL. Great. I'm going to give you a chance to come back on your next highlight, Abrar.

Abrar AbuHamdia:

Okay, for me, for the final highlight, I will be speaking on brain organoids because I worked on induced pluripotent stem cell-derived brain organoids and this area, like, naturally caught my attention because organoid is powerful. They allow us to model aspects of human brain development and disease in a patient's specific genetic background. They represent a transformative platform for modelling Alzheimer's disease and other neurodegenerative diseases. Especially, they can help address limitations of animal and 2D models. They not perfect, of course, but they give us a window into early biological events that are almost impossible to study directly in living humans. And for me, I will actually speak about a poster which titled "Human Cortical Organoids Recapitulate Early APOE4-Associated Immune Dysregulation" by Dr Katlin.

They generated cortical organoids from APOE4 carriers and non-carrier controls and incorporated induced pluripotent stem cell microglia into the system. And what makes this really interesting, that they capture information and capture data at two time periods: early and late, and they found that at four weeks of maturation the organoid did not yet show amyloid-beta or phosphorylated tau-217 accumulation, which was detected later, at eight weeks of maturation. And this gave them a window to examine what happens before visible Alzheimer's disease pathology appears. They then used proteomic analysis to compare APOE4 and control organoid and found that immune-related changes were already present before amyloid and tau pathology became detectable. And for me, this is very important concept. So here we can answer whether immune dysregulation comes first, or maybe they develop secondary to Alzheimer's disease.

Adam Smith:

So, if you could've been in the audience; I don't know if you were watching that live or if you're watching that from catch-up; what questions would you have asked them? Was there any uncertainty in there? Or was that all very clear?

Abrar AbuHamdia:

What I may ask about is whether they think that these immune-related changes, they are responsible for the disease progression, or it are just inclusions, because, actually, we see, for many anti-amyloid, for example, treatment, they don't actually affect the progression of the disease. So, have they thought that maybe this underlying mechanism are responsible for the progression of the disease? And if we targeted them, we may actually. Let me say not prevent but slow the progression of the disease.

Adam Smith:

Yeah, I think that's a good question for all the anti-amyloid therapies. Oh, that's the elephant in the room, isn't it, now? We have the proven ability to clear amyloid, but it doesn't regrow the brain. It doesn't bring back what you've lost, so the target shifts to getting the amyloid out earlier and earlier. But it's interesting then to see how that gets deployed and the other treatments that might go alongside it, so.

Abrar AbuHamdia:

Yeah, we are looking about this underlying mechanism. We can target early stages, okay? And I think, actually, we may target disease in, like, reversible stage. so, we may actually prevent the development of the disease itself. But then after neurodegeneration, it is really difficult. So, currently, they are using stem cell therapy. They get induced pluripotent stem cell, and they differentiate them into neurons, and they implant them in the brain to replace neuronal loss. And they are actually. There are current trials going on Parkinson's disease.

Adam Smith:

That's amazing, and it'd be great 'cause that's going to be what it takes, isn't it? It's to go like HIV treatments and other things. It's not going to be a single drug that will fix everything. It's going to be a complement of different medications, potentially, alongside, you know, lifestyle, which we know works in cancer as well, but it's often that grouping of treatments alongside other things and personalised, as we've said a couple of times over the course of this week. Thank you very much, Abrar. I'm going to pick up on. I'm only going to pick up on one final thing, which we should've, of course, mentioned, the other plenary talk from today, which was Professor Takami Sato, who traced more than 30 years of research into amyloid and tau.

To give a really nice picture of how current Alzheimer's disease treatments and models sit within that, he explained how his early work on pyroglutamate-modified amyloid contributed to the scientific foundation of donanemab. He also highlighted neprilysin, an enzyme that helps clear amyloid from the brain but appears to decline with age, making it a possible target for future prevention treatments. He spent a lot of time at the end talking about newer knock-in mouse models, which may reflect human disease more accurately, but finished with a big warning that licensing restrictions, and he singled out a particular university that we won't mention on the podcast — but go and watch the talk — could be severely limiting access to those mouse models and slowing therapeutic development.

The key takeaways are that basic amyloid research helped pave the way for donanemab; neprilysin is an important target for preventing amyloid buildup; better disease models could improve understanding of the amyloid-to-tau transition; and we need to stop being so protective over mouse models. Share, because we all need them. I think that's all we've got time for today. I would like to thank Cari Randa-Beaulieu and Abrar AbuHamdia, who have both fought through technical problems today. Hopefully, I've edited this and it all comes across incredibly slick, but we have fought through guests not turning up, technical problems and microphone issues. We still powered through, and we hope you enjoy and appreciate this podcast, because it has taken effort this evening. I'm grateful to all of you for sticking with us and listening, and to my brilliant guests. Cari and Abrar, you've been amazing. Thank you both so much.

Abrar AbuHamdia:

Thank you so much for having me in this podcast.

Cari Randa-Beaulieu:

Yeah, thank you. It's always great to rattle the cage about qualitative research. (laughs)

Adam Smith:

So tomorrow, we'll be back with our fourth and final daily highlight show with another group of researchers and one last tour through the studies, posters, and conversations that've been attracting our attention. You can learn more about all of our guests on our website, where you'll find bios on them, and dementiaresearcher.nihr.ac.uk. We've also been putting more AAIC coverage on there, as well, on our website. And of course, you'll find all the full programme and lots more to catch up on at aaic.alz.org. And there is still time to register, as well, for the AAIC For All conference, which is on Thursday, which is designed for any audience of any level of understanding. There'll be something there for everybody, and that's going to be on Thursday. But for now, I'm Adam Smith, and you've been listening to the "Dementia Researcher Podcast." Thank you very much.

Voiceover:

The "Dementia Researcher Podcast" was brought to you by University College London with generous funding from the National Institute for Health and Care Research, Alzheimer's Research UK, Alzheimer's Society, Alzheimer's Association, and Race Against Dementia. Dementiaresearcher.nihr.ac.uk.