Podcast – Alzheimer’s Research UK Conference Roundup 2025

Voice Over:

The Dementia Researcher Podcast. Talking careers, research conference highlights, and so much more.

Rebecca Williams:

Welcome to the Dementia Researcher Podcast. This week we've been to Birmingham to attend the Alzheimer's Research UK annual conference. Stay tuned for all the news and updates from this leading UK event. Hello and welcome to this special edition of our podcast, coming to you directly after the Alzheimer's Research UK event in Birmingham. I'm Rebecca, your host for today, and I'm thrilled to be here to share some of the most exciting highlights that we had from last week's Alzheimer's Research UK conference. So, joining me today, I have three incredible voices who've all been to the event. The brilliant Dr. Beth Williams from the UK Dementia Research Institute in Edinburgh, the equally incredible Gargi Roy from Bristol University, and the equally, equally amazing Donatella Di Rienzo from the ARUK Drug Discovery Institute in Oxford. But before we get started, let's learn a little bit more about our guests themselves. So, kicking it off with you, Beth, what is it exactly that you get up to over at that UK DRI Institute in Edinburgh?

Dr Beth Williams:

So, I'm currently a postdoctoral researcher at the UK DRI here in the lab of Dr Patricio Opazo. We look at synaptic compensation, so the ability for synapses to enlarge and reform after damage. And so, we do a lot of two-photon imaging, a lot of in vivo work is currently what I'm based at doing. And yeah, that's really what I get up to, day to day.

Rebecca Williams:

Yeah, that sounds incredible. I mean, it's such interesting work. I mean, we're going to get into some of the amazing stuff that people are doing at the ARUK conference, but even just speaking to people through this format, it always amazes me to hear the variety of research that gets done around the UK. Onto you, Gargi, what do you get up to in Bristol?

Gargi Roy:

Hi, thank you for the lovely introduction, Rebecca. My name is Gargi Roy, I am working as a specialist technician with the Cerebrovascular Dementia Research Group at the University of Bristol, and I'm currently on a pilot study funded by the ARUK, and I'm looking at parasite injury in Alzheimer's and vascular dementia.

Rebecca Williams:

Well, moving on to last, but certainly not least in that case, Dona, what do you get up to in your day to day?

Donatella Di Rienzo:

Thanks for having me. So, I am a third year DPhil student at the Oxford Drug Discovery Institute, and my focus is on the LDL receptor in the CNS, and as a therapeutic strategy for APOE clearance. So yeah, it's been exciting to work on that target.

Rebecca Williams:

Lovely. Well, I think we got a cracking panel to kick us off, for speaking about Alzheimer's Research UK today. Thank you very much for those little introductions. So, before we get to the standout moments from the conference itself, were any of you presenting? Because I'd love to hear a little bit more about some of your research just from those little snippets we got in the introductions. Gargi, I think you said you had a poster, is that right?

Gargi Roy:

Yes. I presented a poster based on my current research, and it was titled Identifying Novel Biomarkers for Parasite Injury and Alzheimer's Disease. Sounds very wordy, but initially I'm just six months into the research, so I didn't have a lot of data, but that poster did spark a lot of interesting conversations with other researchers in neurovascular Field. And yeah, it also helped me with my confidence to speak to other people in a public space as well.

Rebecca Williams:

It's always so great with the posters you get into such interesting conversations and angles on your own research that you'd have never thought to go into. Could you share, is there any particular conversation you had that gave you some new insights?

Gargi Roy:

Well, I did connect with some researchers who are also working at the University of York, and they're developing this antibody, monoclonal antibody that can go and directly attach to the protein of interest. And instead of doing an ELISA for eight hours, we could figure out proteins in samples within less than 10 minutes. And that was really interesting to know about. And apart from that, at the beginning I was a bit scared that if they asked me something, I don't know about it, then it would be embarrassing. But no, the environment was really comfortable, everyone was really jolly, and nobody judged me if I didn't know anything. So that was a good start.

Rebecca Williams:

That's a great start. I think it's such a common experience, especially for early career researchers, is this fear that we're going to get found out that we don't know everything. And I think it's so nice to be in a community of people where that's totally okay. We know we don't know everything, that's why we're here learning. Fantastic. And Dona, you said you also had a poster?

Donatella Di Rienzo:

Yeah, sorry, I did touch on it a little bit about the LDL receptor, and we know so much from the peripheral perspective, but it's actually one of the principal acceptors of APOE. And as you know, APOE is the greatest genetic risk factor for Alzheimer's disease. So, I have these IPSC derived macrophages and I'm working a lot with actually a very cool E3 ubiquitin ligase called IDOL, which regulates the LDL receptor. So, a lot of my work is to see if we knock out IDOL, what is the effect on the LDL receptor and subsequent effects on APOE uptake and cholesterol homeostasis, and things like that, and obviously inflammation as well.

Rebecca Williams:

Wow, incredibly cool. Are you also in the earlier stages or do you have some results that you can share with us on that?

Donatella Di Rienzo:

Yeah, there has been really exciting results. So also, we have in-house our i3Neurons, these are cortical neurons, and they secrete APOE. And using these pulldowns I have labelled them and measured uptake. And so far, the uptake is increased in the IDOL knockouts compared to the parents, which is what we're expecting, and well, hoping to expect. And effectively, yes, the next stage of this is to start looking at how does this affect cholesterol homeostasis, what is the effect with the lysosomal degradation in our macrophages, and how does this affect inflammation? So, it's starting to make a lot of progress now.

Rebecca Williams:

Amazing. It's so exciting when things start to come together, isn't it? Like getting those results [inaudible 00:06:28] started making a little bit of sense. It's always a joyous occasion I've found as I come to the end of my PhD. And I do believe we actually have a full set here because Beth, you also had a poster.

Dr Beth Williams:

Yes, I did. I wasn't actually taking my postdoc work, so I finished my PhD last summer. And so, I took that, which was quite nice to have a final finished version of what I had spent the last three and a half years doing. And that was looking at the effect of experience on the regional and mechanistic requirements in learning and experience. So, I investigated one side of it, was looking at the intrahippocampal, so dorsal to ventral connections within the hippocampus, and that requirement in a first experience, but then also in a second one. So, what we do is we take animals, we take our mouse model, and we undergo fair conditioning and then they undergo a second fair conditioning, but in a completely different environment, and that's how we can make that first and second experience.

And basically, found that this requirement for this connection has changed. So, you need it for a first but not for a second learning. And that was done using optogenetics. And then the second half of my PhD was looking at the requirement of NMDA receptors. And so, you need your NMDA receptors to learn something for the first time. And it's been proven that you don't need it for a second time. So, we looked at the requirement of these receptors in the APPPS one mouse, which is an early amyloid model, and basically found that they don't do the shift that they still need their NMDA receptors a second time. And then spent a long time trying to work out how we could restore that.

And so, we managed to restore it using time, so shrinking the time between the two events. So, if they immediately go from a test of the first, into the second experience, that forces this shift is what we called it, the shift from receptor dependent to independent. And then the second way we managed to restore it was using optogenetics again, so using a C-Force virus to tag cells that were active during the first experience, artificially reactivating them, and then mice undergo the second experience. And that also fixed it, so that was quite nice to see. So wrapped it up quite nicely.

Rebecca Williams:

Yeah, absolutely, I mean I feel like from the array of research we've heard there, I think it's really indicative of the quality of even just the posters that were at Alzheimer's research UK was incredibly high. I have to say optogenetics is still something that is just absolute sci-fi to me. Every time I see it; I'm just a little bit mind blown. Perfect. Well, let's get on with talking about the conference itself. For those who weren't there, it's a three-day event mostly with UK researchers, but including some absolutely fantastic [inaudible 00:09:21] from some international researchers. And it kicks off with an early career researcher day, which includes a lot of fun science, but as well as a lot about careers. And did you all go to that? Were you able to make that first day?

Dr Beth Williams:

Yeah.

Donatella Di Rienzo:

Yeah.

Rebecca Williams:

Lovely. Well, in that case, I suppose I could ask, could you share maybe a highlight just from that early career day? Maybe Beth, can we start with you?

Dr Beth Williams:

Yeah, so I had a couple highlights from that day. To start with, I think it's always really lovely to see early careers or ECR talks. I think it's lovely to see that other people at similar stages of their careers and all their talks. And then another highlight for me was we had where the day split in two, that we had two separate sessions at different times that I went to the one titled Future of Dementia Research. And that was really interesting to hear about the direction that they think clinical trials might take and drug discovery might take, and where all that's heading. So, I think it was quite nice to be reminded of... You know? At the baseline level of our research, the direction that it's all coming together and going towards.

Rebecca Williams:

Yeah, could you maybe give us a headline? Where is this research going towards, according to this session?

Dr Beth Williams:

I mean, they were sort of talking about the idea of trying to use more inclusive clinical trials, trying to move away from this really niche, just one sole disease, and maybe look at the impact of comorbidities or people who often get taken out of clinical trials who never qualify in the first place. So I think looking towards that, especially with dementia, often exhibiting with so many other comorbidities that it would be quite nice to see the expansion of that and see if we can really try and create future treatments that help more patients who are struggling, who are impacted by disease, rather than this niche small percentage that often get included in these trials.

Rebecca Williams:

Absolutely. I mean, I think we saw from looking at obviously the new drugs that have been approved now for Alzheimer's disease, it's incredible just how small the percentage of dementia patients are actually able to take those drugs. So, I think comorbidities is definitely something that's going to come into play a lot more as that drug development continues. Thanks, Beth. Gargi, how about you? What was one of your ECR highlights?

Gargi Roy:

Yes, so this was my first big conference that I went to. So, first day I was really nervous, but it felt really nice to see people who are at my stage and also get a vision of where I could be later on in life, seeing these beautiful, amazing talks by inspiring scientists. And the introductory talk by FTD brothers, I think Jordan came in, and one thing that really struck me was he said that "Be kind to whoever you see, because you don't know what they're going through." And as a researcher he told us that be persistent with your research, do not give up. And it was really nice to see that what we are doing in the lab will actually have effect on real people lives. And that was really quite inspiring and interesting to know as well. And also Dr. Sophie Moore's her talk on a new technology, on invasive... Sorry, non-invasive, sorry, non-invasive ultrasound technology that can be used for therapies in Alzheimer's and other neurodegenerative diseases. That was quite interesting and new I think, because it can really revolutionise how we treat these diseases going forward in future.

Rebecca Williams:

So, I actually wasn't there for the ECRR day, so what was the headline from the non-invasive imaging side of things?

Gargi Roy:

So, she is working on this technology which can help cross the blood-brain barrier without tearing it apart. Just making force through the blood-brain barrier, going in, and treating the cells, like the glial cells, she is right now working on glial cells, or delivering any sort of proteins or drugs that we might want to deliver into the brain without corroding the blood-brain barrier. So that was quite interesting, and I think that can really revolutionise the way we deliver drugs into the brain.

Rebecca Williams:

Yeah, absolutely. Such a big issue that I think came into the drug development session as well. And yeah, I completely agree about the FTD brothers. I mean, what an inspiring talk we had from them in the main body of the conference as well. There's a family that so many of them have suffered from FTD because they're, I believe MAPT carriers. And it's incredible to see how they've harnessed that energy of seeing their family members go something that was obviously very distressing and harness that into something so positive in order to fuel Alzheimer's research and FTD research forward. It's really incredible to see. Dona, how about you? What did you think of the ECR day?

Donatella Di Rienzo:

Oh, it was fantastic. I would say as a sort of mini highlight, one thing that I really liked that they did throughout the day, was for some of the speakers at the end of their presentations, they would ask, "What's a piece of advice you would give to other ECRs?" And I thought that was such a nice touch, because everybody had something different to say, which was lovely. I think for example, there was one person, I can't remember who it was, but she showed a list of every single grant she's applied for, and she said, "Please don't give up." So of course, there were many highlighted in red that unfortunately she wasn't able to get, but then you can also see the green, and it was pretty much saying, "Don't give up, keep trying." And it was quite inspiring to see. So that's kind of a side note.

Another perk of the ECR day is that you can already start looking at posters, so you get that advantage to start meeting people, which is great. And yeah, also I absolutely love that talk on the ultrasound and the micro bubbles, and I think that's such a powerful technology, because one of the biggest issues that we always have with the CNS, obviously it's meant to be protective, but it's to have penetrating drugs for targets in the CNS. And I think the idea of being able to take these micro bubbles, I think she described them, and having them as a lower wavelength, so not pure ultrasound, I think that's how I understood it, and then being able to apply this and have these micro bubbles come through to introduce these wider pores, I think it's such a great new way of using old technology, if that's the right word, but reshaping the technology that we have, which is fantastic.

Rebecca Williams:

And I love the idea of asking people for advice for ECR, because it's something I always find so valuable, and it's the question I always want to ask, regardless of the context of the talk. So maybe I can turn that back on you. Do you have any advice for ECRs? Maybe we could kick off with you, Beth.

Dr Beth Williams:

Yeah, I mean I think I've added this to my bio, but my biggest one that probably people hear all over all the time is network, network, network. I mean, it always feels really daunting and quite a horrible task to try and do, but everybody, especially at conferences like ARUK are so lovely and so approachable, and everybody really is in the same shoes, that we're all there to try and meet everybody else. We're all there to try and not just see who's doing similar science or similar techniques, but really just to get a feel for the people in research, the people who are doing similar work to us who are just at similar life stages to us, similar career stages. So, I really do just say network, network, network. Speak to everyone, anybody. And you'll never know who in five, 10, 15 years that you'll come back around, and you'll say, "Oh, we met ARUK 10 years ago," and it's fostered this really lovely supportive relationship.

Rebecca Williams:

Yeah, I mean I think it's so true. It's so difficult when we... to go outside of your lab, I always fined. I always want to stick with the people I know, but I think this is why posters are so great, because they allow you for that kind of springboard for conversation, I find so useful for networking. Obviously, you always hear from older researchers say, "Oh yeah, we've been coming to this event for 20, 30, 40 years, and coming and meeting new people every time." So, I think that's a great bit of advice. Dona, how about you? Any advice for ECRs for conferences?

Donatella Di Rienzo:

For conferences, I mean I think the main one is it's going to be very obvious but enjoy it. Go to as many talks as you can, get excited and broaden what you are looking at as well, because you can get very... Well, in my context, I get so focused on one particular thing, the LDL receptor, and then suddenly I get to these events and just my brain expands all over again and I'm learning about the neurovascular unit, which is something I wasn't really paying much attention to. So yeah, I would really say at these conferences, try, and go to the talks that sound, especially in the parallel sessions that maybe sound new as well, something for you to explore.

Rebecca Williams:

Yeah, totally. I mean the number of times I think my favourite parts of conferences have been the talks that I had no idea what even the title meant. So, I completely agree with that. It's a fantastic opportunity to explore out the bubble. And Gargi, what about you? Any last bits of advice for ECRs?

Gargi Roy:

Well, as an ECR myself, and I think I added this in my bio as well, be fearless and grab any opportunity that you can. I mean for me to come to this podcast was a very last-minute decision and I'm glad I could come here. And so yeah, just grab any opportunity you can. Email that supervisor, email that funding body. You never know what happens. Your potential is limitless. You don't know your potential.

Rebecca Williams:

Yeah, I once heard someone say, "Don't talk yourself out of rooms you deserve to be in." And that really stuck with me as a piece of advice because it's so easy for us to talk down the expertise that we have and the research that we've done, but actually we're all pretty impressive and it's okay to embrace that sometimes, I think. Speaking of things that are ludicrously impressive, let's move on to the rest of the conference because the ECR day really was the beginning really. So, let's have a talk about the highlights from the rest of the conference as well. Dona, maybe I can kick off with you. What was one of your highlights from the main body of the conference?

Donatella Di Rienzo:

Well, I think one of my highlights, I wouldn't be surprised if it was a lot of people's, was the 100-plus study. The work was described by Professor Henne Holstege based at Amsterdam UMC. And she addresses a really important question, which obviously we're always looking at risk factors that can potentially lead to Alzheimer's disease. But what is considered almost preventative. And are there individuals out there that are cognitively healthy but over 100? And this is what her and her have done, they followed, I'm not sure how many, but a cohort of Dutch centenarians, they did a wide range of tests. So, they obviously looked at lifestyle, they looked at their genomics, kind of a broad array as to why these individuals are cognitively healthy. And it was fantastic to hear about it. So, for example, their lifestyle, they seem to be from a higher socioeconomic status, they seem to be very educated.

And one thing they mentioned was that they were extremely optimistic, which I thought was quite interesting. And what I quite liked from, because I'm quite focused on microglia as well, is when they were doing the genomics, they found that a lot of these individuals had the PLCγ2 P522R protective variants, which makes microglia slightly more activated. So, the suggestion is that maybe you need a slight increase in inflammation to be considered protective. So that's something she said. And then I'm really sorry, just the last thing, I got a bit carried away. There was one individual, 104 centenarian, who again another focus for me is APOE, this individual is APOE 4/4, which is meant to be very tightly linked to Alzheimer's disease progression, but with this PLCγ2 P522R variants as well is actually cognitively healthy. So, things like this are just fantastic to see the other side of things of can we actually be healthy in ageing and can we be cognitively healthy in the latest stages of our lives? So, the me was the highlight.

Rebecca Williams:

Yeah, absolutely. I completely agree. It was such a great talk as well. So well delivered. But also, they just seem to throw everything and the kitchen sink at this cohort. It's really incredible to see such a rich data set and obviously the analysis they're doing with it coming out with some incredible results, as you touched on Dona. Beth, Gargi, also a highlight for you? Is there anything different you took away from that talk?

Dr Beth Williams:

I mean, it was definitely a highlight for me. I think a couple of my favourite slides, just apart from obviously all the science and the data that they create, was at one point she put up all these pictures of these different centenarians and said, "How old do you think these people are?" And thought maybe in their mid 80s, or something and they're all a hundred plus, and look like they're getting up and going to work every day still, kind of. So loved that. And then I loved the advice, the quotes that they had taken from individuals in the study of... You know? Some of their tips and tricks for, "How have you reached a hundred? How have you stayed so healthy for so long?" And coming out with things like, "Eat lots of onion, eat lots of fish," or "Only drink expensive red wine, never drink white wine."

And you get the classics of, stay away from... No smoking, no alcohol. But I think one of my favourite quotes I think that lived with us for the last few days was, "But not too many women," I think was a really great quote. If I could just imagine that you've got these people in this study who are coming in every sort of six months to a year having these cognitive tests, being really put through the wringer quite a lot of the time, and that's their takeaway from the study. So, I thought it was a fantastic talk, and I thought it was really, really engaging. And like you say, really positive to see at least cognitively resilient individuals are thriving, and that they could teach us definitely something about not just genetic, their different lifestyle factors and things like that. So, really definitely great talk.

Rebecca Williams:

It always really surprised me when you see people who look much younger than they are, it always questions in my mind, "Do they just have this kind of much slower biological ageing process, or is there something unique about the way they're ageing, beyond just this offset of a few years?" I think it really sparks some interesting thoughts for me. Gargi, any last thoughts on that talk, also a highlight for you?

Gargi Roy:

Yes. I asked her one question, asking that, "Are these people regularly active through the exercise?" And she said, "Yes, very well. They are so fit." And that was quite baffling to me because in my family, if I've seen elderly people, after an age, they really become quite like they can't move properly, and that is what I have seen in older people. But to see these people so active and so youthful and it just tells that age is just a number, it's about how you feel. You need to feel 20, you don't necessarily need to be 20. So yeah, so that was really nice.

And also, I think the previous day also we had a talk on I think the Klotho gene and how it is neuroprotective, and then we had this talk where we didn't talk about Klotho , but we talked about the other cellular and molecular basis of staying healthy. Generally, all our projects and mostly all of us are interested in looking at the pathology of the diseases, the risk factors, as somebody said, but we never focus on how to stay healthy. You're only focused on the disease state. So, this was quite a unique perspective.

Rebecca Williams:

Yeah, I mean, just yesterday I went to a talk which was the Cambridge Healthy Ageing cohort and seeing some results from there. And I completely agree, I think our research goes hand in hand, and it's always really interesting to see the flip side of the coin of the people who are ageing ludicrously healthily. This 115-year-old woman with the brain of a 20-year-old, it's really incredible stuff. So, I completely agree there's definitely a field there that we link close to in dementia that we need to do a little bit more collaboration with, maybe. Fantastic. Moving on from that fantastic plenary then, Beth, did you have any other highlights from the conference?

Dr Beth Williams:

Yeah, so I think on the basis of the different breakout sessions, looking at the... there's an advancing drug discovery session with all the latest news of antibody-based therapies. I think it was really interesting to go to that and hear some individuals about their drug work, their drug discovery units, and sort of a little bit tied in with Sophie's talk on the ECR day about trying to find different methods of getting through the blood-brain barrier.

There was a talk from the representative at Roche, talking about the brain shuttle technology, trying to get this antibody into the brain for clearance of amyloid, and how successful that those trials seem to have been and how quickly it seems to have removed amyloid from the brain, and taking what is a relatively large molecule across the blood-brain barrier and not seeing, especially with other antibody-based therapies, seeing large side effects cohorts with quite severe side effects of these drugs. So having minimal to no side effects going on with this technology, with this brain shuttle technology from them. So, I think for me that was really fascinating to see, that even if we are leading towards trying to find these bigger molecules that we think could be really helpful, that there are quite a few different pathways now that we can get across the blood-brain barrier.

Rebecca Williams:

Absolutely, and like you say, what really struck me about that is as effective as it was as clearing amyloid, like you say, these ridiculously low rates of aria, which is obviously something for all the mAbs that have come through so far, this is one of the primary side effects that we've been really concerned about, and I think it was Trontinemab, really, really low levels of aria was really something incredible. Were there any other of the drug discovery talks that you found particularly interesting?

Dr Beth Williams:

I think there was a PhD student gave a talk at the end, talking about their nasal-based approaches for trying to get their drugs into the brain. I think I'm just fascinated about how everyone's getting their things across the blood brain barrier, whereas the different techniques to treat individuals, just delivery I always find really interesting. But their work was really fascinating for SIRNAs to try and get for APOE4, as an APOE4 target. And I think that was really fascinating. Some really in-depth work coming out of drug discovery labs was really I think my takeaway from that session.

Rebecca Williams:

Yeah, absolutely. It seemed to be a big thing this time, is crossing that blood-brain barrier, and now that we have drugs that we know that are really effective at clearing amyloid, and you see these pie charts coming up quite a lot now of all of these drugs that are starting to make their way through the drug discovery pipeline. I think you're absolutely right. It's getting that implementation, getting it across the blood-brain barrier is going to be an increasingly important problem that we're seeing so many innovative ways to try to try solving. Did anyone else go to any different parallel sessions? Gargi, any parallel sessions you particularly enjoyed?

Gargi Roy:

Speaking of the drug discovery talks, this just reminded me of the debate that we had, that is amyloid cascade hypothesis, the way to cure. And I think that sparked really interesting conversation afterwards as well. So, after the debate on the second day when we had Dr. Nick Faulks talk about the available treatments, I guess we are really heading towards a cure potentially. Maybe not one cure. The main takeaway from that debate was there's just not one cure, there might be multiple cures, it's just we need to find which one is the fastest one.

Rebecca Williams:

Yeah, absolutely. I think I heard a conclusion of the amyloid, is it the cure, or is it the way to a cure? The overarching things seem to be it's a way to a cure rather than the way to a cure. And I think it was really interesting seeing the poll of whether people agreed or disagree with that statement. At the end it was pretty much 50/50, wasn't it? Which was quite funny to see, of just a complete split if whether people agreed or disagreed that amyloid was the way forward. Dona, how about you? What was another one of your highlights?

Donatella Di Rienzo:

Yeah, just to sort of tag in with also that debate, I think something that was really important that was mostly addressed by Dr. Claire Howard, she said that, and she kind of related it to MS where there were drugs coming out quite early on that still needed work, but what she was saying is this is just the start. This will just pave the way for newer and better drugs. And the kind of take-home message from me over the two days in regard to these amyloid targeting therapies, is that these are for the first time disease modifying.

They're doing what they were supposed to, which is they are clearing amyloid. And that is something that patients have waited for, for such a long time, is some kind of disease modifying therapy. And the really nice turn on this is maybe they're not the final cure, but they are the start. And that's something that everybody working on Alzheimer's disease research has waited for a long time. So, I think that was one of... for me is how I felt by the Wednesday is just excitement that we have a start, and it can just keep getting better and better thanks to these treatments that we have so far.

Rebecca Williams:

I think it's... should I say, it's definitely the case that amyloid is a way forward. And I love the phrase that one of the people on the panel used, which was its a in the Armour, which I thought was a lovely way to see it. But then equally some of the questions that we saw coming in from the audience were, "If it's so effective at clearing amyloid, why are we still seeing these quite small by comparison effects on cognition?" So, I think it's really interesting debate still open there. Beth, do you want to weigh on this? What did you think of the amyloid debate?

Dr Beth Williams:

One thing that the debate did, and I think that ARUK from this conference and when I've been in the past, is always really good at doing was shifting that focus back on patients, and is this actually going to make a difference for patients? And I think that's one of the things mentioning about how, yes, these drugs are effective at clearing amyloid, and that they can take the levels of amyloid in the brain right back down to pre amyloid positive levels. But if that's not having an effect on cognition or it's not really slowing it to any kind of substantial amount, bringing that back to patients, is it then worth the possible side effects of these drugs?

And I think that that's something that was spoken about on the debate. I think it's always very lovely to have a clinician involved in these discussions, that they get to tell us and they get to speak about their lived experiences with talking to these patients, talking people directly involved, and how with these therapies not approved on the NHS, people are upset about that, you've got other people seeking a private route in order to gain access to them. And is it actually going to make that much of a realistic difference to their lives?

I think one positive of these amyloid clearing drugs I think has been the look forward treatments coming towards dementia is... I mean it paves a way of if you can catch the disease early enough, if we can really go for early diagnosis, that maybe that might be the turning point that, a lot of these trials take people with a really solid dementia diagnosis who are quite advanced into the disease progression. And I often wonder if that's why you don't see that much of a cognitive benefit from them. But yeah, that debate I think was a really interesting addition and I think really fired home the importance of the work, and I think bringing it back to the patients and having the talks from the FTD brothers in the morning, and then on the ECR day we had another talk from a family whose father had been diagnosed with early onset dementia. And so, I think ARUK is always really good at reminding us of who is this all for.

Rebecca Williams:

Yeah, absolutely. And I completely agree. I think having those kind of panels with the academics, with the clinicians, and always with the patients themselves and their caregivers at the forefront, is something that the ARUK conference is particularly good at, particularly motivating for. Gargi, you mentioned Nick Fox's plenary as well. Was that another one of your highlights?

Gargi Roy:

Yes, I did find it a bit complicated for me because I did find... But it was quite interesting and also how he engaged all the audience in it. He's a lovely speaker, the way he speaks is beautiful. So, I think that's also something I need to learn from him. And apart from apart from Nick Fox, also one more talk that really stuck with me was Dr. Amanda. Because I am working on biomarker development, she and her team is doing a lovely work at the biomarker factory at UCL. And potentially, going forward, we can just take a drop of blood from her finger and can-do diagnosis. That was really interesting to me, because at this point, we have no proper diagnosis for Alzheimer's, it's only the cognitive symptoms that we are looking at, but there's no clinical diagnosis. So going forward, if we do have a clinical diagnosis, we can treat them also better with better drugs. So, treatment and diagnosis should go hand in hand like that, I feel.

Rebecca Williams:

Yeah, absolutely. And like I say, I think that earlier diagnosis, getting people earlier into trials, as you were saying, Beth, its only people included at the minute with that firm dementia diagnosis, it's going to be interesting to see how that landscape changes as we get better diagnosis. Any other talks on the diagnostic aspects that people enjoyed?

Gargi Roy:

I think one more talk before Dr. Amanda was on how we can check the levels of p-tau in blood, and that can be a potential diagnostic marker for Alzheimer's. Also, the P-tau test is available in NHS as far as I remember, but there are certain criteria, that because you will get p-tau as you get older, so there are certain criteria’s you need to follow before you actually go for that test. So, I think awareness regarding those kinds of tests and when you should go for something like that is also particularly important, I think. And I think this should go out a lot to the general public as well so that they know when to go for certain kind of tests or treatments if they feel something is wrong with them.

Rebecca Williams:

Yeah, absolutely. I mean another session that I actually really enjoyed was the pub patient and public involvement session. Did anyone make it to that?

Gargi Roy:

Yes. Yeah, that was really, really engaging. And also, they gave us these cute postcards where we had to write how we are going to engage with the public and patient in six months, and then they said that they're going to post it back to us in our offices. So, I'm really looking forward to that.

Rebecca Williams:

Yeah, I mean patient involvement I think is something that is so challenging to kind of get set up, but it's so rewarding when you get it there. Getting the actual words from patients' mouths to check that the research that we're doing is the research that they want to be done. And same with caregivers and with the general public. And it was a really good reminder that we need to make sure that we're honing our research according to what the people actually want to see from the research we're doing. Fantastic. All right, I'm going to bring it together now with your one highlight above all highlights from the ARUK conference. I'm going to start with you, Dona. What was your absolute ultimate highlight?

Donatella Di Rienzo:

I think I have to go back to the 100-plus study. It was really for me, such a unique way of doing research, and I found it really heartwarming. And just my small is the exhibitors as well. They were absolutely... It's always a really splendid feature of conferences, and I think ARUK had a wide selection. And a little shout-out to the Women in Neuroscience UK. They are someone I wasn't aware of before, but they're a talented group, so I follow them now. But yeah, I left feeling positive by the last day. So that would be the highlights for me.

Rebecca Williams:

Fantastic. I have to back Women in Neuroscience UK. They're a fantastic organisation, but in particular they do wonderful stickers. They do little stickers that say, "Synapse sisters," and "This is what a scientist looks like." They make me smile absolutely every time I see them. Beth, how about you?

Dr Beth Williams:

I think yeah, also the 100-plus club, but I think also away from the science, I always love the community feel at ARUK, I think it's a really great conference. I think it hits that really nice spot of being big enough that there's such a variety of science, but small enough that it doesn't feel quite so overwhelming and that you're missing out on not being able to attend a lot of things. So, I do have to say that the community feel, it's definitely one of those conferences that I recommend early career researchers to go to. If you've got anything to do with dementia, I think it's definitely one to try and get in your calendar if you can.

Rebecca Williams:

Absolutely, yeah, it's always fun at conferences, getting to catch up with people, especially when you're all in this shared space of dementia. I think it's really great. And I think the interactivity with the audience through Slido and through the questions, and for some people directly with polls, I think for example in the amyloid debate, was really, really great to get this idea of this audience interaction, I really enjoyed as well. And Gargi, what about you?

Gargi Roy:

Yes, I think the debate was something that will really stick with me for a long time. And as Dona touched upon, the various sections that they had, like women in neuroscience, different biotech companies, and also ARUK themselves. So, I saw this interesting maze board where they were trying to replicate how cerebral blood flow occurs in the brain. And I think they had some really cool apps also for educating children and older people about those sections of the brain that are affected, different 3D brain models. And those were really interesting to see, and I think people will engage and people will find signs not intimidating, but interesting, if they take these to the local public. So, I think lots of interesting conversations, lots of interesting people. For my first conference was a bit overwhelming at first, but I think I really felt comfortable as the days went on. And yeah, I really kind of miss it now a bit. It feels a bit mundane to come back to work, but yeah, I'm looking forward to it next year as well.

Rebecca Williams:

Yeah, I bet. And I suppose we should also give a shout obviously to the prize winners at the ARUK conference in the Laura Pulfer Prize, the Jean Corsan Prize. There were some fantastic speeches from the prize winners as well. Any particular highlights from those guys?

Dr Beth Williams:

I think for me, the winner of the David Hague Prize, Dr. Ian Harrison, his work on the glymphatic system. Glymphatics has always been one of those things that I've heard about but never really understood. And I thought his talk was really great at not only the advancements that they're making within their lab and that their use of the glymphatic system for treatment and clearance, but also the history of the glymphatic system itself and how it's actually... in the grand scheme of science, this relatively new-ish environment, to be working with. So, I thought that talk was excellent.

Rebecca Williams:

Yeah, could you give us, maybe for those who didn't see, because I agree, it was a fantastic talk. Could you give us maybe a little 62 second summary of his results?

Dr Beth Williams:

I mean, I'm not going to do it anywhere near as much justice as he could do it himself or anybody who works in glymphatics, because it's not something I do at all. But they've been working, one, that how does this glymphatic system work, putting traces through the CNS and sort of having imaging to see where across the brain it's going. And I believe they use these traces to see where across the brain the glymphatic system is flooding through, and then trying to harness this power of increasing the outtake of dangerous proteins... Not dangerous proteins, but aggregated proteins in the brain.

Rebecca Williams:

Yeah, I always try and explain too when I'm doing science, communicating with children and trying to explain why sleep is so important, I'm trying to explain to them this idea of getting rid of stuff in the brain, and in my head I'm always thinking of glial cells with little mops and buckets, but I think he explained it in a much more accurate way than glial cells with mops and buckets. And I say the glymphatic system is something that so rarely I think gets the attention it deserves, and really interesting how it could potentially be used from a therapeutic angle, I thought was great. Any other highlights from the prize winners?

Donatella Di Rienzo:

Yeah, the Jean Corsan Prize. So yeah, that was awarded to the PhD student with the best scientific paper. And I thought it was really special that her paper was published in nature on the same day that she got the prize. So do check that out online. Did I say her name, Dr. Ashling Giblin? Oh. Dr. Ashling Giblin. She's based at UCL, and she spoke about her work with these polyunsaturated fatty acids, also known as PUFAs, in the context of neurons. And she was able to show that they are protective in FTD and ALS, based on these neuronal lines that they had that best recapitulate that disease.

And it was really quite collaborative because there were elements of lipidomics that were done to show which PUFAs were being altered in these disease relevant models. And then they found that incidentally, they used a dietary intake of those, I think it was linoleic acid. They did this dietary intake, but it wasn't having as much as an effect as actually overexpressing fats one and two I believe it was, which are actually the enzymes that will do the necessary conversions of the PUFAs. And with that, they show this really significant improvement on survival. So, it's a great paper again, from my perspective where I really am interested in lipid metabolism and things like this. I particularly enjoyed it, and I think it's great that there are these really special prizes throughout the conference to address these kinds of accomplishments.

Rebecca Williams:

Yeah, I completely agree. We also obviously had the poster prize, which went at the end of the conference. Were there any particular posters that you liked on your wonderings around ARUK?

Gargi Roy:

I think I definitely liked the poster, the girl who got the prize for the poster, her work was on how exercise can elevate BDNF levels in your brain. And even though she has tested only healthy cohorts right now, going forward, if we can test the effect of exercise on patients, that is quite interesting to me. And also, one of our lab members from the Cerebrovascular Dementia Research Group, Oliver Milner, he also got one prize, and he has been investigating the relationship between microbial activation and cerebrovascular injury in Alzheimer's. And it was quite inspiring to see him get the prize because he's one of my mentors, he has set me up in the lab in cell culture. And seeing him give such a lovely talk and get that prize was also quite inspiring for me.

Rebecca Williams:

Yeah, absolutely. I can imagine. There were so many fantastic posters. I think it's hard to narrow it down. Any favourites for you, Beth, or Dona?

Dr Beth Williams:

I don't know if I ever can pick a favourite. I always find it so difficult to vote for my favourite poster at conferences. I think where everybody's work is so diverse, I feel like it feels unfair almost to pick almost a particular field that should win the poster prize. I mean, there were a couple of people from my lab who took posters. Jessica Willshaw here, she took one to look at the collaborative between slices and in vivo work of synaptic compensation, and the quite nice storytelling of the effect of Aβ in slices and the effect that has on synapses and spine density, and then converting that into the mouse model and doing the same thing and seeing the same effect in vivo. So, her poster, as a little self plug for our lab, was always really lovely.

There's somebody I've met a few times, Nicole Byron, based out of Strathclyde, she was looking at calcium signalling in sleep, I believe. And so, her poster was really fascinating. As somebody who never can understand calcium spikes, and it always takes me far too long to wrap my head around what I'm looking at, she did a really excellent job with her poster as well.

Rebecca Williams:

Absolutely. Any for you, Dona?

Donatella Di Rienzo:

There were. I would say three come to mind, but they're all incredible. One of those posters that I really liked was by Oliver Milner. I think he did both a presentation and a poster, and it was about these capillary associated microglia. And are they actually causing an issue in Alzheimer's disease? Are they affecting the astrocytic feet? What is their phagocytosis potential like? So, I thought that was really interesting. Again, a sort of self group plug as well, is Hannah Dobbs. She's doing some magnificent work with also microglia and understanding lipid metabolism in Alzheimer's disease. So, microglia tend to accumulate to lipid droplets and there's still a lot to understand about these. So, she's setting up this CRISPR screen to identify genes related to this LD accumulation. And then another one was Dr. Clara Musi, I think. And she was talking about senescence in microglia. Again, sorry, there's clearly a theme here. But yeah, so she is looking at senescence in iPSC derived microglia over quite a long culture. So over six months saved to start looking at the relation between ageing and senescence. So, for me, those were my highlights.

Rebecca Williams:

Yeah, fascinating. There's so many, and it was such a nice poster space as well for walking around. I said I had my own poster, it was really lovely, some of the conversations and questions that got asked really helped me kind of look in a new light at some of the work that I'd been doing, which was very, very enjoyable. Fantastic. Well, I think we can all agree the Alzheimer's Research UK conference was a great mix this year. I really enjoyed. Just the variety of talks on offer, I think were fantastic. I think the parallel sessions from public and patient involvement, all the way through to drug discovery, to omics, to fluid biomarkers, to the cardiovascular unit. We just seemed to cover so many different angles.

And I think the interactive components with the audience, we touched on the amyloid debate, but also Nick Fox's plenary where he was asking the audience about what the impact of dementia, mild, also they would have on your life. What if it was a spouse? And comparing that to some of the decision-making being done right now with the NHR and NICE in the UK. Obviously whether these drugs are being included on the NHS I think was incredibly relevant. And as someone who has to try and communicate to lay audiences what advances we're seeing right now in the field of dementia, it was an incredibly valuable conference, I think, to get that kind of information across. So, thank you all very much for your highlights.

And that brings us to the end of this special episode covering highlights from the Alzheimer's Research UK Conference in Birmingham. A huge thank you to my amazing guests, Dr. Beth Williams, Gargi Roy, and Dona Di Rienzo for sharing their wonderful insights and expertise. And also, a big thank you to Alzheimer's Research UK for Organising another, I think we can all agree, pretty stellar event. Let's say the variety of stuff on offer was just really fantastic to see.

It's been great to hear again and kind of reminisce about this latest research that we've heard as well as the passion driving this field forward, both from the academics but also these amazing personal stories from, we've touched on the FTD brothers, but also families at the ECR day. It's always important to keep those patients at the fore, and I say I think including clinicians in the discussion as with the amyloid debate, it's always a wonderful thing to do for that as well. If you've enjoyed this discussion, don't forget to subscribe, and share the podcast, and of course, keep an eye out for more updates from the world of dementia research. Thank you for listening, and until next time, I'm Rebecca Williams and you've been listening to the Dementia Researcher Podcast. Goodbye everyone.

Dr Beth Williams:

Bye.

Gargi Roy:

Bye.

Dr Beth Williams:

Bye.

Voice Over:

The Dementia Researcher Podcast was brought to you by University College London, with generous funding from the UK National Institute for Health Research, Alzheimer's Research UK, Alzheimer's Society, Alzheimer's Association, and Race Against Dementia. Please subscribe, leave us a review, and register on our website for full access to all our great resources. Dementiaresearcher.nihr.ac.uk.