ISTAART Relay Podcast – Immunity and Neurodegeneration PIA

Voice Over:

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

Dr Hamid Sohrabi:

Hello everyone and thanks for joining us. I’m Hamid Sohrabi and I’m an Associate Professor of Psychology and Neuroscience at Murdoch University in Western Australia. I’m a sitting committee member of the Reserve, Resilience and Protective Factors of the Professional Interest Area PEER at Alzheimer’s Association. Today I’m delighted to be talking with Dr. Louise Ince from the University of Texas at Austin. Hello, Louise.

Dr Louise Ince:

Hi, thank you, Hamid. Yeah, I am Louise Ince and I’m a postdoc at the University of Texas at Austin in the USA. And I’m here today representing the immunity and neurodegeneration PIA, which I’ve recently been elected as the postdoc representative on their committee.

Dr Hamid Sohrabi:

Fantastic. That was my first question, indeed, that you just answered it. Can you please tell us a little bit about your own research and what brought you to dementia research?

Dr Louise Ince:

Absolutely. I had a roundabout way to get to dementia research. I’m a neuroscientist by training. I did my PhD at the University of Manchester in the UK. Somehow got a PhD in Neuroscience by looking at lung inflammation, but we were working on how this is regulated by the circadian system, which is driven by the brain and signals there. And then I moved to Munich, Germany to do a postdoc looking at adaptive immunity and how immune cells travel around the body. That lab then moved to Switzerland. And then I recently moved to Texas to follow up on essentially how immune cells migrating and innate immunity within the brain influences cognition and behavior. And that brought me a little closer to dementia through aging and how cognition and behavior changes in this stage of life.

Dr Louise Ince:

And the real shift into dementia research was prompted by essentially seeing how elderly patients and patients with dementia experience this exacerbation of symptoms if they get a systemic infection. So, we know that there’s interactions between the peripheral immune system feeding into the brain, and then this drives those changes. And in some cases, it’s reversible and in some cases, it changes the trajectory. I’m really trying to understand how immune function changes with aging and with dementia and essentially what we can do to try and slow disease progression.

Dr Hamid Sohrabi:

Fantastic. And I see that you have been quite interested in circadian rhythm and how it may affect the inflammatory markers in the brain. Can you tell us a little bit about that also?

Dr Louise Ince:

Absolutely. I’m also on the Sleep and Circadian PIA, I’m not on their executive committee, so I’m moonlighting this role, I guess today. The circadian system is really these daily fluctuations. We have these oscillations of 24 hours that’s driven by the rotation of the earth. And there’s daily rhythms in things like stress hormones, like cortisol, melatonin rhythms, sleep-wake is probably the most obvious one that most people are aware of, but there’s also rhythms in immune function. In my postdoc work, we looked at simply the numbers of immune cells in your blood. Depending on the time of day that you take that blood sample, there’ll be different amounts of immune cells. And this can have really significant consequences down the line. If you have an inflammation or a vaccination, for example, can also be regulated by time of day. And how this links to aging is really that these rhythms tend to break down in older age, and we are really looking at how this then influences neuroinflammation and behavior.

Dr Hamid Sohrabi:

Okay. That’s fascinating. In that sense then, what are the main hot topics these days in your research area?

Dr Louise Ince:

Yeah. We have a few. On the circadian side, I would say timing of therapy. Chronotherapy is a big one. On the inflammation side, I’d say there’s three. We are really looking at the role of peripheral versus central nervous system immune function. That role of cells migrating into the brain versus the role of immune cells within the brain. So, microglia, astrocytes, and things like this. There’s also a big move for biomarkers looking at prognostic and diagnostic biomarkers on the immune side. And I think also, especially for our group, the relevance of COVID-19 and those. Our PIA I think has been great at writing. We’ve done a series of roadmap papers for each of these, but if any of those take your interest, I’m happy to talk a little bit more about those.

Dr Hamid Sohrabi:

Yeah. Fantastic. Yeah, definitely. I think because of the impact of COVID-19 on our inflammatory markers, I wonder if you can just tell us a little bit about how this potentially can increase the risk of Alzheimer’s Disease there.

Dr Louise Ince:

Absolutely. I think that we’re too early to really say that just because COVID has been not around for that long, although it feels like forever at times. But yeah, it is too early to have done any of these longitudinal studies, but certainly, there’s great work looking at, on the one hand, how lockdown measures and social isolation have influenced some of the effective side of Alzheimer’s and aging, so behavioral symptoms, but also as immunologists, we’re absolutely aware of and very concerned about how this degree of inflammation or latent virus can influence predisposition to disease. There are quite a few pieces of work looking at how multiple hits essentially predispose to neuroinflammation and neurodegeneration. And often this is on the earlier side. So, things like inflammatory insults in utero, for example, so for the pregnant mother having inflammation and then a second hit later on in life.

Dr Louise Ince:

But if we are having a huge wave of inflammation now as adults, how is this then going to affect if we then further down the line, have additional inflammation and modulate neuroimmune function?

Dr Hamid Sohrabi:

Great. And potentially you might be also interested, or you could tell us a little bit about the relationship between gut microbiome and neuroinflammation and how they could be developed.

Dr Louise Ince:

That’s very interesting. That’s not something that I’m personally working on. I think the gut microbiome stuff is so interesting. It’s really difficult. All of these taking samples, and, in some cases, they do fecal transplants, which I think is super gross, but really kudos to the people that are doing it because they’re getting really interesting results. There’s been a lot of work on this, on how the gut-brain access can modulate cognition and equally how the brain modulates enteric functions if there’s gut problems in people with neuroinflammation. And again, this also feeds back to circadian rhythms. If these rhythms degenerate, this also impacts upon the rhythms of bacteria within your gut, which impacts upon how they interact with your feeding schedules, which can then modulate cognition and behavior.

Dr Hamid Sohrabi:

Okay. No, that’s great. Thank you. That was very informative. My next question for you is how your PEER support your field of research?

Dr Louise Ince:

Yeah. Immunology is such a broad field and there’s quite a few of us in our PEER. I think we’re on about 650 or so, so it’s a really good size group with a lot of different interests. I mentioned before we’ve got peripheral immune cells, like T and B cells and monocytes, and then we’ve got brain resident cells and macroglia and astrocytes, so it’s a lot of varied interests. There’s a lot of people to keep happy, but I think we do a really good job. We try and do, I think, an online seminar at least every month, if not every other month. We’ve done a few of these. We do those roadmap papers. These are discussions with smaller groups and then publish papers essentially on… It’s a review of what we do know, but then really pushing it to like, okay, what don’t we know? And how do we address that? I think as an early career researcher, these are great because you can just get your next experimental ideas from some of these discussions, which is awesome.

Dr Louise Ince:

We also do specifically for younger researchers, we have a newsletter. I think we do it three times a year. We have a break over summer. But in these, there’s at least three to five junior researchers that are spotlighted. You can absolutely self-nominate. So, if you don’t know anyone in the PIA yet, just send an email, nominate yourself. And these are profiles both of your career path, what research you’re doing. And also, some background information, a bit more about you as a person just to get to know you a little bit better. I’d say those are the main things. We do also have some collaborations with other PIAs. We did a methods club with the PEERs PIA that Adam is working with. Also, journal clubs and Q and as with the authors, which I think is awesome. It’s a great opportunity to really discuss with the people who did the work, how they got there, any trials and tribulations with getting that paper across the line.

Dr Hamid Sohrabi:

Yeah, that’s good. That’s good. And in terms of your committee and the PIA that you are involved in, can you tell us how is it organized and what’s the group of people that are involved in and who are the chairs and committee members and so on?

Dr Louise Ince:

Yeah. We have a really well-organized group. I think we’re really, and it’s certainly one of the best-organized committees that I’ve seen. This is really nice. We have a bit of time at the end of the meeting to get to know each other a bit. It’s a really nice atmosphere I have to say. And we have a chair, we have a vice chair, and then essentially that role shifts into the next session. Whoever was vice chair becoming chair, and then we have an immediate past chair role. This ensures a nice continuity between sessions. We keep that momentum going, which is great. We’ve got a steering committee. This helps to direct our goals, push towards those roadmap papers, and the subcommittee for this. We have a communications chair who organizes, I think, all of our emails, the newsletter, and anything like this. And a programs chair who schedules all of these webinars coordinates with other groups to schedule these, also running the sessions at AAIC. We organize and pitch some of these.

Dr Louise Ince:

And we’re trying to do some sessions within other conferences. We are quite nice in that we’ll straddle neuroscience, but also immunology. So, trying to pull knowledge from both sides to really get the best scientists into the group. And then, my role… I’ll come to that one. My role is as a postdoc member, we have two postdoc members and students, and they were also elected. There’s two of us essentially representing the goals and interests of more junior researchers. Not only, I think, junior in the sense of career stage, but also people who are new to the field because again, we have people entering the PIA from the immunology side, like myself, but also from the neuroscience side. So, trying to represent everyone really. And also, a shout out to the two ISTAART staff that sit in on our meetings. They keep us to time and also hold us very accountable for deadlines. ISTAART have been great through this.

Dr Hamid Sohrabi:

That’s very good that you’ve got such a very well-organized PIA, as you’re saying. And in that sense then, how can early career researchers get involved in your PIA?

Dr Louise Ince:

Oh, it’s super easy. I think the Pia is really welcoming. The first thing I’d say is join ISTAART. Or if you’re thinking of attending AAIC, I think they’re still doing the package where you can join, you can register for AAIC, and join ISTAART. I did that last year and I think it was because if you did that AAIC, the virtual content was basically free. So, I was like as a postdoc, you don’t want to spend too much. I registered for the virtual AAIC, joined ISTAART, looked through the PIAs just to see what else you’re interested in. With that, I joined the immunity one. I joined the sleep and circadian one and the PEERS, the PIA to elevate early career researchers, I think. Adam can correct me if that’s not the right acronym. I joined those three.

Dr Louise Ince:

And then with that, signed up to attend webinars, experience this. And then I really wanted to host an online seminar. I wanted to look at the role of adaptive immunity in neurodegeneration. I pitched that to the team, got to host an online seminar. You can really go from like nothing to key members relatively quickly. It’s all about your motivation, how much you want to get involved.

Dr Hamid Sohrabi:

That was fantastic. In terms of the PIA that you are involved in, can you tell us a little bit about the aims for this coming year and what targets are you aiming to achieve?

Dr Louise Ince:

Yeah. Our PIA, I think, was really productive last year. We had a great year writing. I think we have four roadmap papers that were published, potentially one, I think in review as well at the moment. We also fostered some more collaborations. It’s really trying to maintain that momentum into the next year. We’re currently discussing which other papers to target next, what are the hot topics? So yeah, going down that line. We also hosted sessions at AAIC. Again, trying to like to build a nice session that brings people in from all sides. And with that, also looking at other conferences, looking at immunology conferences, looking at neuroscience conferences, trying to branch out and build that network across other research topics.

Dr Louise Ince:

And I think again, just trying to link with the different PIAs as well. We’d love to do more work with the PEERs Pia for early career researchers. Again, do some more of these journal clubs and methods club because I think with immunology, often it seems like a bit of a scary topic to get into, but it’s really not. And I think our PIA is great for bringing people in and giving them the skills and knowledge to address the questions that they want to address. I think that’s where we’re going for this year.

Dr Hamid Sohrabi:

No, that’s good. That’s good. And are you presenting at AAIC?

Dr Louise Ince:

Sadly, no. I can’t go this time. I’m a virtual attendee this year, but I’ve been through the schedule. There’s a lot of really cool stuff. Obviously, the PIA will be there at the PIA Day. I think our slot is at 2:00 PM on Saturday, but there’s basically stuff on every single day. And I would strongly recommend on Sunday there’s a session on neuron clear interactions with Malu Tansey. This is going to be a great session. There’s stuff on glial biology biomarkers, which is going to be a really hot topic. This one is on Tuesday, I think. And microbiome, we also touched on, this one I think it’s Wednesday. But check through the schedule. I think it’s great. You can type in like inflammation, immunity, and it’ll bring up all of the relevant stuff.

Dr Hamid Sohrabi:

Fantastic. Thank you for that. Now it’s time to end today’s podcast recording, but before we go, I have a final question for you. What advice can you give to any aspiring researchers out there who are thinking of potentially joining the Dementia Research team?

Dr Louise Ince:

I would say absolutely go for it. Join ISTAART, join the PIAs, get involved. At the same time, learn how to say no effectively and nicely. This is still something that I struggle with, but I think there’s a lot of pressure, especially on early career researchers to do all the things, but the sooner you can identify what’s important to you and what’s important to your career and then follow those as strongly as you can, then that’ll save a lot of stress further down the line. But yeah, absolutely go for it.

Dr Hamid Sohrabi:

Okay, fantastic. Thank you very much, Louise, for taking the time to join us today. It was a great pleasure to hear about your research and what you have done and what you’re planning to do with the PIA. And hopefully, we can have more researchers joining the PIA that you’re involved in and also other PIAs that could be of interest to the new researchers. That’s it for today and I should say goodbye to you and the listeners.

Dr Louise Ince:

Thank you, Hamid. Thank you, everyone.

Dr Hamid Sohrabi:

Bye.

Voice Over:

Thank you for listening. You’ll find profiles on today’s panelists and information on how to become involved in ISTAART on our website at dementiaresearcher.nihr.ac.uk and also at als.org/ISTAART. We’ll be back tomorrow with the next recording in our ISTAART PIA Relay podcast series. Finally, please remember to like, subscribe, and leave a review of this podcast through your website, iTunes, Spotify, SoundCloud, and in all the other places you find your podcasts. Thank you.

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