Latest / Dementia Researcher Vodcast / ADPD 2026 Conference Highlights - Part Two

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ADPD 2026 Conference Highlights - Part Two · Dementia Researcher Vodcast

• 0:00
  (upbeat music) - [Voice Over] The Dementia
• 0:01
  Researcher Podcast, talking careers,
• 0:03
  research, conference highlights,
• 0:05
  and so much more.
• 0:07
  - Hello and welcome
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  to the Dementia Researcher Podcast.
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  Today's episode is coming to you
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  from ADPD Conference in Copenhagen,
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  where researchers from around the world
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  have gathered to share new findings
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  on Alzheimer's disease, Parkinson's disease,
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  and other related neurodegenerative conditions.
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  (upbeat music)
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  I'm Louise Serpell,
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  a Professor of Biochemistry from
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  the University of Sussex,
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  and I'm delighted to be hosting today's show.
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  This week, the ADPD Conference
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  has brought together scientists
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  working across the full spectrum
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  of neurodegenerative research
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  from molecular mechanisms
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  to biomarkers and clinical trials.
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  Across the few days,
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  there have been hundreds of talks
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  and posters, so rather than
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  trying to summarise everything,
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  today, we're going to focus on
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  a few highlights that really
• 1:00
  stood out to our guests during the meeting.
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  Joining me are three people
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  who have been exploring this conference,
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  Athina, Lauren and Sofie.
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  And I'm going to ask them each to
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  introduce themselves and tell you
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  a little bit about their background.
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  (upbeat music)
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  Before we begin, could I ask each
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  of you to briefly introduce yourselves
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  and tell listeners what area of
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  research or work you're involved in.
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  Athina?
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  - Hello, I'm Athina Grigoriou
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  and I'm a second year PhD student
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  in Dr. David Koss's lab at
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  the University of Dundee in Scotland.
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  So we are working on DNA damage,
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  so basically understanding
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  the role of DNA damage in dementia
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  with the Lewy bodies
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  and then compare it with
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  other neurodegenerative diseases
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  such as, Alzheimer's disease.
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  And specifically, I'm looking
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  into the role of alpha-synuclein
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  in DNA damage repair pathways.
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  And what comes first, basically.
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  Yeah, that's me, thank you. - Thank you.
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  And Lauren?
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  - Okay, so hi, I am Lauren O'Neill.
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  I'm also working at the University of Dundee
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  alongside Athina in Dr. David Koss's lab.
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  So my project is looking at elucidating
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  the mechanisms or specifically,
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  where alpha-synuclein is gonna
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  bind on the human genome
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  in dementia with Lewy bodies
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  and my background in mitochondrial biology
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  and also my interest in DNA damage.
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  I kind of wanna, for my project
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  ship them these two together to look
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  at mitochondrial DNA damage specifically
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  and see if there's alpha-synuclein
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  you can also bind
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  in the mitochondrial genome. - Oh, fantastic.
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  Sounds really interesting.
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  And lastly, but not least, Sofie.
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  - Yeah, hi everyone, I am Sofie Frandsen
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  and I am a senior research scientist
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  at a small biotech company called, Vesper Bio,
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  which is actually based here in Copenhagen.
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  So this year's ADPD Conference
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  is in my hometown, so that's very nice.
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  So I am a pharmacist by training
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  and have done a PhD
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  focusing on Parkinson's disease.
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  And right now, I am working at Vesper
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  who are developing small molecules,
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  a sortilin inhibitor to increase
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  the important protein in the brain
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  called, progranulin, which is
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  decreased in a lot of
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  neurodegenerative diseases such as,
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  FTD, Parkinson's disease,
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  and also in mood disorders.
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  So yeah, very nice to be here. - All right,
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  thank you very much, Sofie.
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  So welcome everybody.
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  So how have you found
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  the conference so far, enjoyable?
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  - Very. - Yes.
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  - Brilliant. - A lot of talks,
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  a lot of good posters.
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  - Yeah, it is very big.
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  I think it's one of the biggest
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  conferences we've been to,
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  but was talking for myself, yeah.
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  - Well, just to give the listeners
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  a bit of a flavour for it,
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  it's, I think five or six parallel sessions.
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  Hundreds and hundreds of posters,
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  loads of exhibitors, it's a lot.
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  It's a lot it to try and cover it all.
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  - Yeah, I think there was over 700 posters
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  per shift and there's two shifts,
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  so there's a lot to go around, yeah.
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  - So you have to pick carefully.
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  - Yeah. - Don't you?
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  - And the prior sessions were like,
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  there's one in the morning,
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  there's two in the afternoon,
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  and I dunno, it was like eight talks
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  per session, per prior session.
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  - So I think the app helps a lot
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  as well because then you can get
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  an overview of which talks,
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  you can highlight them as your favourites
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  because otherwise, there's so many.
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  - [Prof Louise] Yeah. - They had an AI summary
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  as well, so you could go back
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  and get a report of what the main findings
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  of the research or each talk.
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  That was really good.
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  It was really helpful.
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  - Yeah, yeah, that's good.
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  So let's start with Athina.
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  I would like to know
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  what you found most interesting.
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  I think you've picked out one
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  particular topic you're particularly
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  interested to do. - Yeah.
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  - What about it?
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  - Sure, I'll go on.
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  So I really like this talk.
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  It was by an associate professor
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  named of Dettmer and he's
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  a associate professor like I said
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  at Harvard Medical School
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  and in the States.
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  And what he presented is
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  because it's relevant to my work,
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  that's why I really liked it.
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  But what he presented is that
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  he argued that the phosphorylation
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  of alpha-synuclein serine 1:9,
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  which we all know
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  is the pathological protein found
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  in dementia with Lewy bodies,
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  may actually have a normal reversible
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  physiological role during synaptic activity.
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  So he showed a number of,
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  well, a lot of figures,
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  a lot of data, and one of the things,
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  but what they use and is published now
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  is in cortical neurons,
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  they showed they're increasing
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  the network activity using picrotoxin,
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  it raised this phosphorylation
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  at serine 1:9
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  without damaging the total protein,
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  total alpha-synuclein levels.
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  They've done this in vivo
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  and what they've shown again is that,
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  under environmental enrichment
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  also increased phosphorylation
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  of the alpha-synuclein serine 1:9.
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  And that anyway concluded that there
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  is a physiological role of the phosphorylation.
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  Doesn't mean it doesn't play any role
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  in disease, but it shows
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  that there is normal activity.
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  Then they went and tried knock-ins,
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  knock-downs, and mutations
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  and what they showed is that
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  in a knock-in mouse model where
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  it prevented the phosphorylation,
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  it showed that there was a redaction
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  in an impaired hypercomplexity
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  and cognitive deficits against suggesting
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  this physiological phosphorylation,
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  it contributes to the normal synaptic
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  transmission and plasticity.
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  Then he also showed some very,
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  it's new and published data,
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  which was really interesting to see.
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  And what they did is that
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  they introduced a phosphomimic.
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  So it was mimicking phosphorylation
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  and again, they could see all these
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  impairments in the hippocampal
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  and the long-term potentiation
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  and the Y-maze performance.
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  He said that it raises two interpretations.
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  One that there is a dynamic
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  reversibility of phosphorylation
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  that is required or whether
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  the mimic that they use,
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  it does not function as a true
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  phosphomimic in cells and it behaves
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  more like a loss of function.
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  Yeah, and then I'll keep on going,
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  how about that.
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  There's some last things I wanna say
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  about it is that then they
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  used the the PLK2 inhibitor,
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  which we know that is an inhibitor
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  that it could inhibit the phosphorylation
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  of serine 1:9 of alpha-synuclein.
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  And again, they showed that
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  when they did this,
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  they actually restored the function
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  and the neural network
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  and everything, which was really cool.
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  So overall what they concluded is
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  that alpha-synuclein serine
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  once an phosphorylation
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  has an important physiological
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  activity dependent role of the synapses
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  and it's distinct from its pathological
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  accumulation in Lewy bodies.
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  - That's so interesting. - And it is amazing.
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  - It's really interesting to think
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  that the proteins that misfold
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  in neurodegenerative diseases
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  also have an important function
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  and perhaps, you know,
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  this hyperphosphorylation
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  or phosphorylation of alpha-synuclein,
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  and tau, that actually it's part of
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  a functional role and then somehow,
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  that regulation goes wrong
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  and that's maybe what leads to the pathology.
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  So it is fascinating.
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  - Yeah, exactly, that's why
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  we liked it because
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  compared the pathological role
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  and the physiological role.
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  So it actually shows that
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  it will be good to look into another way.
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  Like we just look things in a different
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  perspective when we are doing this.
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  Not think that this is just pathology,
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  you know, there might be
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  something else there that we don't know.
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  So it would be good to be
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  looking both the positive, I think,
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  and the negatives the same where
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  that makes sense. - This is going to be
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  so important of course when we go
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  to therapeutics, if you're just going
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  to clear out this particular phospho
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  type of alpha-synuclein
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  and then actually, it's really important,
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  it sounds like.
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  And that sounds like they did some
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  really robust experiments to show that
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  that actually has a really functional role.
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  - Yeah, exactly.
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  And he was just saying that
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  this is just preliminary,
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  but just preliminary data
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  and published preliminary data
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  showing this, it means that
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  there is more to come, you can see that
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  there is a trajectory there.
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  - Thank you, Athina,
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  that really came across
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  how excited you were about it. - Yeah.
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  - That's fantastic, thank you.
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  So Lauren, do you want to tell us
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  a bit about what you found really
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  interesting at the meeting? - Yeah, of course.
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  So as I mentioned before,
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  I come from a mitochondrial background.
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  So one of the symposiums was looking
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  at mitochondrial pathways
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  and so I was instantly drawn towards
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  that session, one talk in particular
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  who was by Professor Sarah Berman,
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  she's a assistant professor
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  at the University of Pittsburgh.
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  She was looking at essentially
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  this complex one PET-binding protein,
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  it binds to complex one
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  in the mitochondrial respiratory chain.
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  So the first complex oxidative phosphorylation
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  and essentially, using this
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  radioligand that binds to complex one,
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  they're able to see the relative abundance
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  of complex one in Parkinson's disease patients
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  and people who have dementia Lewy bodies.
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  So this was answering the research
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  question of disease stratification.
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  So I think typically, I mean,
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  I definitely thought this years ago
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  prior to my PhD, you know,
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  Parkinson's disease is Parkinson's disease,
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  but it seems that you have these
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  different phenotypes that,
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  you know, they're all different
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  types, but under the same umbrella
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  of Parkinson's disease of the shared pathology.
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  So this talk was quite interesting
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  because it really did kind of,
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  it really questioned that narrative of,
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  you know, different types of Parkinson's
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  disease with different specific phenotypes.
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  So the approach that they used was
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  using this 18FBCPPEF PET,
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  I know, the radioligand,
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  so I'll just say that.
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  And the binding is relative
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  to the abundance of complex one.
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  And what they found is
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  as the disease duration
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  of Parkinson's disease and dementia
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  with Lewy bodies ensued in these patients,
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  the binding of complex one actually reduced.
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  So that's kind of supporting
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  a lot of the literature that
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  we've known for many years now knowing
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  that we have complex one dysfunction
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  in these alpha-synuclein endocrinopathies.
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  But it was interesting that
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  it was dependent on disease duration
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  and it was also particularly
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  interesting that they found that
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  those that were actually
• 12:01
  complex one deficient were less likely
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  to like be tremor heavy for their phenotype.
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  Whereas, those who weren't deficient
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  in complex one were more tremor
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  heavy in their phenotype.
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  So it's two kind of distinct phenotypes
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  based on their complex one pathology,
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  which I found particularly interesting.
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  And something that I found that really,
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  it struck me quite strongly
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  because it does kind of relate
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  to some of the things that
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  I did for my PhD project as well,
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  is that in the earlier stages,
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  they found that there was actually,
• 12:33
  an initial increase
• 12:34
  in a peak in complex one binding.
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  So it's telling us that
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  there could be an initial compensator
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  mechanism going on first
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  and then as pathology ensues,
• 12:43
  the mitochondria become overwhelmed.
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  And you know, as we get an increase
• 12:47
  in reactive oxygen species
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  and a lot of stress, it just starts
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  to downfall as pathology progresses.
• 12:54
  - Really interesting.
• 12:55
  So what I remember
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  and Parkinson's disease
• 12:58
  is not my area of expertise,
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  but complex one was highlighted
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  particularly because of
• 13:03
  the drug-related induced
• 13:06
  Parkinson's disease, wasn't it?
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  - Yes, so I think they found that
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  in human, I think it was like
• 13:11
  an accidental sort of thing.
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  So there were these people
• 13:14
  who had been taking this,
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  it was like a opioid, it was the MPTP
• 13:19
  and then the metabolite MPP+,
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  it was actually a complex one
• 13:22
  inhibitor and it mimicked
• 13:24
  and created these Parkinsonian
• 13:27
  phenotypes in the people
• 13:28
  who've taken this drug.
• 13:29
  And we also know that from animal models
• 13:31
  and cellular models, they add in rotenone,
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  which is a complex one inhibitor
• 13:35
  also induces this mitochondrial
• 13:38
  phenotype associated with Parkinson's
• 13:39
  disease, but also, the motor symptoms
• 13:41
  in these animal models as well.
• 13:43
  - And so are they motor dysfunction heavy,
• 13:48
  those particular models or less so?
• 13:51
  - I don't actually know.
• 13:51
  So this is something that
• 13:52
  I found really interesting from this talk
• 13:54
  'cause I hadn't come across that before.
• 13:57
  Just the case of something
• 13:58
  so small as a mitochondrial complex,
• 14:00
  the deficiency in that can cause
• 14:02
  just such a difference
• 14:03
  in the phenotypic presentation.
• 14:05
  Yeah, I thought that was amazing.
• 14:08
  - It's really fascinating, isn't it?
• 14:09
  And I think what you
• 14:10
  said at the beginning about
• 14:11
  Parkinson's disease, not really
• 14:13
  just being one condition
• 14:15
  is so important at the moment
• 14:17
  because I think there's been a lot of
• 14:19
  publicity about understanding
• 14:21
  these neurodegenerative diseases
• 14:22
  as heterogeneous conditions
• 14:24
  with different protein misfolding
• 14:26
  and different mechanisms within them
• 14:29
  that we really need to try and pinpoint.
• 14:31
  So personal medicine is gonna be
• 14:33
  so important to sort of work out
• 14:35
  and stratify people into the right categories.
• 14:38
  - And just to add on that,
• 14:39
  I think that's also very general theme
• 14:41
  at ADPD is these biomarkers
• 14:43
  that is advancing a lot. - Yeah.
• 14:46
  - But it's both to stratify the patient
• 14:48
  and to identify them early
• 14:50
  but also, to understand the complexity
• 14:54
  of the Parkinson's disease
• 14:55
  and Alzheimer's disease.
• 14:57
  And there are actually a lot more
• 14:58
  comorbidity as well across these disorders
• 15:02
  and also just with neuropsychiatry
• 15:04
  and so on, so I really think
• 15:06
  it's important that we understand.
• 15:07
  - Yeah, I was just about to say,
• 15:09
  there's a lot of like co-pathologies
• 15:12
  and that every single protein,
• 15:14
  for example, alpha-synuclein,
• 15:16
  you can have the alpha-synuclein
• 15:18
  how it forms and aggregates
• 15:20
  within dementia, with Lewy bodies,
• 15:22
  it's different and Parkinson's
• 15:23
  is different in AD.
• 15:24
  So there's actually understanding
• 15:26
  the different co-pathologies
• 15:28
  and those proteins is,
• 15:30
  it will be really important for
• 15:32
  future treatments, I guess, yeah.
• 15:34
  - And as you mentioned,
• 15:35
  I think the way forward is
• 15:36
  personalised medicine
• 15:38
  so hopefully, someday, yeah. - Yes, maybe in time
• 15:43
  for you young people. - Yeah.
• 15:45
  - Hopefully hope, we really, really hope.
• 15:47
  Yeah, yeah.
• 15:48
  So Sofie, would you like to
• 15:50
  tell us what you learned? - Yes.
• 15:52
  So as I mentioned, I really have
• 15:55
  always been into Parkinson's disease
• 15:57
  and that's been my PhD focus and so on.
• 16:00
  So I would just take a step back
• 16:01
  and first talk about a talk by
• 16:05
  Daniel Kremens who is a co-director
• 16:08
  of Parkinson's Disease
• 16:09
  and Movement Disorder Centre.
• 16:11
  And he talked about the clinical
• 16:13
  needs in Parkinson's disease
• 16:15
  and how many unmet needs there are
• 16:18
  and we're not really treating everything.
• 16:20
  And especially, he talked about these
• 16:23
  non-motor symptoms
• 16:24
  that are not treated in patients
• 16:26
  and mentioned the cognitive impairment
• 16:28
  and a lot of patients,
• 16:30
  they also have hallucinations and so on.
• 16:32
  And this is just not treated,
• 16:34
  right now, levodopa is still
• 16:37
  the golden standard and has
• 16:39
  been that for 50 years
• 16:41
  and it works good initially,
• 16:43
  but it doesn't with time
• 16:46
  and may also be related to gut
• 16:49
  dysfunction, which is very common
• 16:51
  in Parkinson's disease patients.
• 16:53
  So I really think he put
• 16:54
  like good perspective that
• 16:57
  we need some disease modifying treatments
• 16:59
  and we need to understand the treatment
• 17:00
  better and we need new targets
• 17:03
  and we need to not only treat symptomatic.
• 17:08
  And in that regards,
• 17:09
  I also found both a poster
• 17:12
  and also, a talk on a non-dopaminergic
• 17:16
  target called, the p75 receptor,
• 17:19
  which is also a target we are looking at
• 17:22
  at Vesper Bio, so maybe,
• 17:24
  I'm also biassed about this,
• 17:27
  but the question is that targeting
• 17:29
  this neurotrophic or DAF receptor
• 17:32
  signalling improved neurodegenerative
• 17:34
  diseases and I was very glad
• 17:37
  and happy to see that it actually
• 17:40
  has some positive outcomes.
• 17:41
  So there was a talk from a lab
• 17:43
  in Montreal, so in Canada
• 17:45
  and then there was also a talk by
• 17:48
  Frank Longo who works at Stanford University
• 17:51
  and as I recall it, I hope it's correct,
• 17:53
  but he's developed small molecules
• 17:55
  to this target, himself
• 17:57
  and he has shown that
• 17:59
  very positive signals on cognition
• 18:02
  and motor behaviour in mice,
• 18:04
  but also, saw some reduced tau pathology.
• 18:08
  So also has some good indications
• 18:10
  in both Alzheimer's disease
• 18:12
  and Parkinson's disease
• 18:13
  and also, some good effects
• 18:15
  on somatic proteins.
• 18:17
  So I think it just really gives us some,
• 18:20
  yeah, that we can find some new mechanisms
• 18:24
  and some hope that we can treat
• 18:27
  more disease modifying
• 18:28
  and also in the progression stage
• 18:31
  and not just symptomatically.
• 18:33
  - It makes me wonder, you know,
• 18:35
  what p75, is it p75? - [Sofie] Yes.
• 18:38
  - What it does because
• 18:40
  is it something like p62 or...
• 18:43
  - It actually is,
• 18:45
  you can call it a DAF complex
• 18:46
  it actually sits in a complex
• 18:47
  with sortilin, which is our target.
• 18:50
  And so it actually causes apoptosis.
• 18:54
  So if you go and inhibit it,
• 18:56
  you of course, reduce apoptosis
• 18:58
  and then you mature
• 18:59
  the pro-neurotrophins or neurotrophins
• 19:02
  and then you induce the cell survival.
• 19:07
  Yeah, so it can be an indication
• 19:08
  of both FTD, Parkinson's disease,
• 19:12
  Alzheimer's disease and so on.
• 19:13
  So again, this very broad
• 19:15
  target for neurodegenerative disorders.
• 19:18
  - And do you know what triggers
• 19:19
  that pathway that goes
• 19:21
  through sortilin and p75 yet?
• 19:23
  I mean, is it the protein misfold,
• 19:25
  which is what I go to or... - It could be.
• 19:29
  Yeah, yeah, so it's pro-neurotrophins
• 19:32
  that bind to this sortilin p75 complex.
• 19:37
  So yeah.
• 19:39
  Yes. - Really interesting.
• 19:40
  So you're basically
• 19:41
  rescuing the cell survival. - Exactly, yeah.
• 19:44
  So you're reducing the apoptosis,
• 19:47
  but you're also inducing the cell survival.
• 19:50
  So I think that's a good way to go.
• 19:53
  - That sounds like a really
• 19:54
  interesting strategy,
• 19:55
  completely different maybe
• 19:56
  from some of the other ones. - Exactly, but I think
• 19:58
  that's very promising to see
• 20:00
  that all these very new promising mechanisms
• 20:04
  and targets to help these diseases.
• 20:07
  - Yeah, so I was thinking,
• 20:11
  one of the things that struck me
• 20:12
  at this meeting has been the emphasis
• 20:15
  on biomarkers been fascinating.
• 20:18
  And there were a few talks
• 20:19
  where they talked about diversity
• 20:22
  and whether those biomarkers,
• 20:24
  I mean, the one that's been
• 20:25
  very publicised is tau p2 and p7.
• 20:29
  - Yeah, yeah. - And whether those
• 20:31
  are suitable for biomarkers
• 20:34
  in other populations 'cause
• 20:36
  there is an emphasis on
• 20:37
  western populations generally.
• 20:39
  And I just wondered if any of you
• 20:41
  have picked up anything about that
• 20:42
  in terms of other cohort studies
• 20:45
  where they're looking at that.
• 20:48
  - I think we've been to a couple talks.
• 20:51
  So yeah, like you just said,
• 20:54
  they focus on p-tau217, but
• 21:00
  this was another talk,
• 21:01
  it was on the same biomarkers
• 21:03
  like session, but they picked up
• 21:05
  on other phosphorylation sites
• 21:07
  on the tau protein that they say
• 21:11
  that that could be used as a biomarker.
• 21:13
  So I think the other one was p264,
• 21:16
  if I'm not mistaken.
• 21:17
  Dunno if you remember. - I can't remember
• 21:19
  exactly which one it was. - I think it was 264,
• 21:20
  if I'm not mistaken. - Sounds familiar.
• 21:22
  - Yeah, well, it is on a different
• 21:25
  side of the protein,
• 21:27
  but they showed the use
• 21:28
  and number of techniques,
• 21:29
  I can't recall all of them right now,
• 21:31
  but they showed that that could also
• 21:34
  be used with a biomarker
• 21:35
  and that it comes early in disease.
• 21:39
  You can see there's a lot of people
• 21:40
  who are shifting and trying
• 21:42
  to find other biomarkers or like
• 21:44
  use other different like experiments,
• 21:48
  yeah, to understand anyway always.
• 21:52
  - Yeah, so that's gonna really
• 21:54
  help us with this personalised medicine,
• 21:56
  isn't it? - Yeah.
• 21:57
  - But we are really at an
• 21:59
  early point in biomarkers,
• 22:01
  but it's quite exciting.
• 22:02
  - Yeah. - They found this
• 22:03
  particular one that seems to work
• 22:05
  really well for at least,
• 22:06
  western population. - Like a very important
• 22:08
  point that you did raise though,
• 22:09
  you know, we're looking
• 22:11
  just at the west right now,
• 22:12
  it's very important to make sure
• 22:13
  that this is kind of
• 22:14
  an overarching thing that
• 22:16
  could help everyone around the world.
• 22:17
  And if it isn't then,
• 22:18
  you know, we need to work harder
• 22:19
  for this personalised medicine
• 22:21
  to really make sure that,
• 22:22
  you know, it's not prioritising
• 22:24
  the people that we've just
• 22:25
  focused on this particular
• 22:26
  mutation and modification,
• 22:28
  you need to be helping
• 22:29
  everyone who's suffering.
• 22:30
  - Yeah, and from a mechanistic point
• 22:31
  of view, it's actually really interesting
• 22:33
  'cause if you've got a biomarker
• 22:34
  that seems to work in one population
• 22:36
  and not in another,
• 22:37
  then it's really surprising, isn't it?
• 22:39
  Because then you think, well,
• 22:40
  actually maybe that isn't the mechanism
• 22:42
  of the disease and you need to
• 22:44
  open your mind a little bit more.
• 22:45
  Like you were saying about
• 22:47
  these other targets where you
• 22:48
  can think about upstream targets
• 22:51
  that are really important.
• 22:53
  - Yeah, and I think,
• 22:56
  it's hopeful to see that the techniques
• 22:58
  are also evolving in biomarkers.
• 23:00
  There's a lot of multi-omics posters
• 23:03
  up there, a lot of talks
• 23:05
  on fluid biomarkers.
• 23:06
  So I think the field is also evolving,
• 23:08
  which is great because it really
• 23:09
  gives us a better understanding
• 23:11
  of the disease and also just,
• 23:13
  yeah, identifying the patients early.
• 23:16
  And we need to do that because right now,
• 23:18
  we identified them very too late
• 23:22
  when they have already evolved
• 23:23
  the motor symptoms, for example,
• 23:24
  in Parkinson's disease,
• 23:25
  but we know they actually
• 23:27
  evolved or the disease occurs
• 23:30
  initially 10 years or approximately
• 23:33
  before they have the motor symptoms, so.
• 23:35
  - Yeah, it was also just to
• 23:37
  kind of build upon the point
• 23:38
  that you'd mentioned before,
• 23:40
  kind of how we were talking
• 23:41
  about there's not always
• 23:42
  just kind of one type of disease.
• 23:43
  You have different types.
• 23:44
  So I wonder if that kind of
• 23:46
  comes into, maybe, it could be that
• 23:49
  say p-tau217 is, you know,
• 23:53
  kind of common in the west for say
• 23:55
  like GWAS studies of what we see,
• 23:57
  but then it could be that, you know,
• 23:58
  there's another particular phenotype
• 24:00
  or like sub-Parkinson's disease
• 24:01
  or DLB that is more associated
• 24:03
  with other genes that are seen
• 24:04
  in other parts of the world as well.
• 24:06
  So really highlighting that.
• 24:08
  Yeah, it's very different,
• 24:10
  but very important to address all.
• 24:13
  - And just to add on that,
• 24:14
  there were actually some talks,
• 24:15
  obviously, there were a lot to go to,
• 24:17
  but I've seen the titles
• 24:19
  and there were a lot of studies
• 24:22
  that they were based, for example, on the east.
• 24:25
  So also there was specific
• 24:26
  like Chinese studies or like Amsterdam
• 24:30
  or well, Amsterdam is, yeah,
• 24:31
  still west, but there were like
• 24:33
  in Africa and all this.
• 24:35
  So there are initiatives now that
• 24:37
  they're making all these studies
• 24:40
  in other populations to try
• 24:41
  and understand whether
• 24:42
  what we see in the west
• 24:49
  and whether that relates
• 24:50
  back to those populations.
• 24:52
  So there is stuff going out there.
• 24:55
  - [Prof Louise] Yeah. - Yeah, it's just
• 24:57
  bringing it all together.
• 24:58
  - Yeah, and then that also
• 25:00
  makes me think about,
• 25:02
  there were a few talks focusing
• 25:04
  on women in terms of particularly,
• 25:07
  Alzheimer's disease.
• 25:08
  I'm not sure if there's
• 25:09
  a change in preference
• 25:10
  in terms of Parkinson's disease.
• 25:12
  And I wonder if you found that
• 25:15
  there were any talks on that,
• 25:18
  because it seems really important
• 25:19
  that we're focusing on sort of
• 25:22
  classifying people and stratifying
• 25:24
  the data to try and work out,
• 25:26
  you know, that hormones may have an effect.
• 25:29
  - Yeah, so we know from,
• 25:33
  so I mean, there probably was
• 25:35
  for dementia Lewy bodies
• 25:36
  and Parkinson's disease,
• 25:37
  but in dementia Lewy bodies,
• 25:38
  there's an increased prevalence
• 25:40
  in the male population.
• 25:41
  So I think there was one talk, actually,
• 25:44
  I can't remember specifically what it was,
• 25:45
  but it kind of raised the idea that
• 25:46
  there could actually just be
• 25:47
  sex differences in synaptic activity,
• 25:49
  which could then predispose
• 25:51
  to different pathologies
• 25:52
  because we know that there's links
• 25:53
  between hyperexcitability,
• 25:54
  near inflammation, downstream,
• 25:56
  mitochondrial dysfunction
• 25:57
  that can then be this vicious cycle.
• 25:59
  So it's really,
• 26:01
  I think very, very interesting,
• 26:02
  especially because a lot of the work
• 26:03
  that has probably been done years
• 26:05
  and years ago would've been on male mice
• 26:07
  and you know, it wouldn't have
• 26:08
  been fully representative
• 26:10
  of the female population,
• 26:11
  obviously, Alzheimer's disease being
• 26:14
  most prevalent in women, yeah. - I think that's
• 26:17
  still the case,
• 26:19
  I think you are more aware of it,
• 26:21
  but it's mostly male mice
• 26:23
  that are used in research.
• 26:24
  And I think we really need to shift
• 26:26
  and have both female and male
• 26:28
  because as you mentioned, more females,
• 26:31
  they get Alzheimer's disease. - Yeah, yeah.
• 26:33
  - Yeah, but also, yeah,
• 26:36
  talking about patients and so on.
• 26:38
  Just taking a step back,
• 26:39
  what I thought a lot about
• 26:41
  during this conference is that
• 26:43
  there's a lot of cool science
• 26:44
  and advanced techniques and so on,
• 26:46
  but we are not really thinking
• 26:48
  about the patient perspective.
• 26:50
  And I actually came across a poster
• 26:51
  yesterday by Jacqueline Shapiro
• 26:54
  from something called, Cure GRM,
• 26:57
  which is patient advocacy organisation
• 27:01
  who raises focus on
• 27:02
  FTD patients with the GRM mutation.
• 27:05
  And she actually had a poster
• 27:07
  where she told her family story
• 27:10
  and had a lot of photos with
• 27:13
  her family and who had unfortunately,
• 27:15
  had FTD also because it's very genetic
• 27:19
  disease and I think it was so strong
• 27:21
  and it was a very personal storytelling.
• 27:24
  And I just think we need to remember
• 27:26
  that without the patient voices,
• 27:29
  they really drive the awareness,
• 27:31
  but also the research because
• 27:32
  we need them to donate a lot.
• 27:34
  And I think sometimes,
• 27:35
  I talk to her and she was like,
• 27:37
  "I just feel like a number sometimes."
• 27:38
  And I really think we need to focus
• 27:41
  or just remember
• 27:43
  why are we doing what we're doing
• 27:44
  because of course, we know it's important.
• 27:48
  I think she had a very important point.
• 27:50
  - That is a really excellent point.
• 27:52
  I was going to ask you
• 27:53
  about programme, Lauren,
• 27:54
  'cause you mentioned it, didn't you?
• 27:56
  And I know, yes, that there's
• 27:58
  a variant form that causes FTD.
• 28:01
  - Exactly. - And yeah, I'm surprised
• 28:05
  that there aren't more patients
• 28:08
  or carers sort of involved in this meeting,
• 28:11
  but then it is quite
• 28:12
  sort of in depth high science. - Yeah.
• 28:17
  - It is, but I think it's important
• 28:21
  'cause you know, there were sessions
• 28:24
  that were like spread out
• 28:25
  or there was other, you know,
• 28:28
  obviously, we had some breaks,
• 28:30
  so it would be really nice,
• 28:31
  if on those breaks, we had carers
• 28:33
  talking or even patients like being around.
• 28:37
  I think that will make everyone
• 28:39
  understand and basically,
• 28:41
  recall why I'm doing this,
• 28:43
  why I'm doing research.
• 28:45
  And yeah, it's really nice
• 28:48
  'cause we've seen thousands exhibits,
• 28:51
  there were a lot of exhibitions
• 28:53
  like that we went to during the breaks
• 28:56
  where it be really good if you had one stand.
• 28:58
  If it's just, yeah, just one stand there
• 29:01
  where people talking about their experience,
• 29:04
  especially the carers, I guess,
• 29:06
  it's really hard for them,
• 29:07
  let's just not forget them.
• 29:08
  It's not just the patients,
• 29:09
  the carers as well.
• 29:11
  - I think it's important
• 29:11
  that they have a voice, especially
• 29:12
  for public engagement and patient engagement.
• 29:15
  You know, letting them have a say,
• 29:18
  you don't want them to feel
• 29:18
  like a number statistic, you know.
• 29:20
  - [Prof Louise] Yeah, yeah. - You wanna keep them
• 29:21
  updated with where the research is going.
• 29:24
  - And the genetic forms are obviously,
• 29:26
  incredibly difficult because people
• 29:27
  actually follow their parents
• 29:31
  being ill and declining,
• 29:32
  but then know that they have the gene too.
• 29:35
  So it's really shocking
• 29:36
  to have to live with that.
• 29:38
  I can't even imagine, so yeah.
• 29:41
  - Yeah. - And yeah, that makes
• 29:42
  it so important then, doesn't it?
• 29:43
  - Yeah, a 100%.
• 29:44
  And I think you also mentioned
• 29:46
  this Sofie, about, you know,
• 29:47
  catching, well, not catching,
• 29:49
  but you know, determined presymptomatically,
• 29:50
  that is the most important part to look at.
• 29:53
  And it is interesting that even
• 29:55
  for Parkinson's disease, Alzheimer's,
• 29:56
  dementia Lewy bodies,
• 29:57
  you see these changes that go
• 29:59
  unnoticed like decades before.
• 30:01
  And even, especially
• 30:03
  when you were talking about
• 30:04
  the gut and the microbiome,
• 30:06
  how that can actually have a big role
• 30:08
  in actually the onset
• 30:09
  of Parkinson's disease especially.
• 30:13
  Yeah, considering how many years
• 30:14
  it is prior, I think it's very important
• 30:16
  to really hone in on these presymptomatic
• 30:19
  and prodromal diseases.
• 30:21
  - Absolutely, and then we might
• 30:22
  be able to identify people
• 30:24
  we can treat early enough. - Yeah, that's the goal.
• 30:26
  Yeah, there was a striking code,
• 30:29
  I actually took Lauren a photo,
• 30:32
  it was the Michael J. Fox Foundation
• 30:34
  and they had Michael J. Fox on the poster
• 30:38
  and he said, the Parkinson's disease
• 30:41
  and cure, we're gonna find
• 30:43
  the Parkinson's disease cure
• 30:44
  brain in order to do that is
• 30:46
  because we're all gonna work together.
• 30:49
  So he said, "The reason why
• 30:51
  we're gonna find the cure is
• 30:51
  because we're all working together."
• 30:54
  And that striked me.
• 30:56
  I was like, okay, this is really nice.
• 30:59
  So I guess, that actually made us
• 31:03
  think that we need to publish
• 31:04
  what we're publishing,
• 31:05
  we need to tell other scientists
• 31:08
  and scientists, you know,
• 31:09
  need to talk with each other
• 31:10
  in order to, you know, share the insights,
• 31:13
  and share the thoughts
• 31:14
  and how we can like go forward
• 31:16
  with this so we can get closer-
• 31:18
  - I think that's very important, yeah.
• 31:20
  - And also just to communicate
• 31:21
  the negative data as well. - Yeah.
• 31:23
  - Because I think that's
• 31:24
  also been a problem in the field.
• 31:25
  And I think in regards to that,
• 31:27
  I think the Novo Nordisk,
• 31:30
  the Evoke talks, they were also very good.
• 31:33
  I think it was very inspiring
• 31:35
  and very clear communicated,
• 31:37
  but also very transparent how
• 31:39
  they communicated negative results
• 31:43
  and were just very honest.
• 31:44
  And I think that's so
• 31:46
  important for the field as well,
• 31:47
  because we also learn a lot
• 31:50
  from negative results. - Yeah, exactly.
• 31:53
  - I've also been to a talk yesterday,
• 31:55
  it was not my area,
• 31:56
  but it was about how A beta 42
• 32:00
  and A beta 40, they get degraded in the liver.
• 32:03
  And the first slide the girl had on,
• 32:06
  it was all the studies
• 32:08
  and all the papers that came out.
• 32:10
  Some of them were saying,
• 32:11
  "Oh yes, that is true."
• 32:12
  And then it was like,
• 32:14
  "Oh no, it's not.
• 32:15
  And then, "Oh yes."
• 32:16
  So you could see like the different papers.
• 32:18
  And then she went on to talk
• 32:19
  about her research
• 32:21
  and how she found that A beta 42
• 32:23
  gets the greater faster in the liver
• 32:25
  compared to A beta 40 and all this,
• 32:28
  but she showed that
• 32:29
  there's still this debate out there.
• 32:32
  Yeah, which is really good
• 32:34
  because this is how we're gonna
• 32:36
  address the questions, I guess.
• 32:37
  - Yes, so that openness,
• 32:38
  I was really, really informed
• 32:40
  by the Evoke study on the GLP-1 inhibitors.
• 32:43
  I just thought that the way,
• 32:44
  it was a real exemplar of how
• 32:46
  a company who presumably
• 32:48
  have put an enormous amount of money
• 32:49
  into these trials have actually
• 32:52
  offered to share the data,
• 32:54
  to publicise exactly what they've done.
• 32:56
  And perhaps, this will lead to
• 32:58
  something in the future,
• 33:00
  we don't know, but for them
• 33:02
  to have really talked about it,
• 33:03
  I think it's fascinating.
• 33:05
  I mean, it seems sort of
• 33:06
  plausible that it might be a good target,
• 33:10
  but obviously, not in that trial.
• 33:12
  And so interesting to see
• 33:13
  what will happen next in that area.
• 33:16
  I just hope that they keep being open.
• 33:19
  - Yes, I agree. - Yeah, I mean,
• 33:21
  the best thing would be, you know,
• 33:23
  like a repurpose in a drug
• 33:24
  that already exists, I suppose,
• 33:25
  you know, there's actually evidence for,
• 33:28
  I think it's metformin,
• 33:29
  the diabetes drug and it's actually
• 33:31
  reduced in those who have diabetes
• 33:33
  and that are on metformin
• 33:35
  there's a reduced incidence
• 33:36
  of Alzheimer's disease.
• 33:38
  So I think even if it's not just
• 33:40
  neuroscience, but everyone collaborating
• 33:41
  and everything that we know,
• 33:42
  you know, and yeah.
• 33:45
  - Yeah, so the talk we went
• 33:47
  this morning by Doug Orsland, yeah,
• 33:50
  he was- - Who was it?
• 33:52
  - Doug Orsland, I think, yeah.
• 33:55
  I think, yeah, so yeah.
• 33:59
  Well, I've seen his talk before
• 34:02
  once in another conference
• 34:03
  and it was really interesting.
• 34:04
  So we just rushed this morning
• 34:05
  to get here to see his talk.
• 34:06
  But he was talking about
• 34:08
  the new perspectives in dementia
• 34:09
  with Lewy bodies and Parkinson's disease
• 34:11
  and all the clinical trials
• 34:13
  that this happening.
• 34:16
  And I think they've also used,
• 34:17
  was it Metformin that they were using?
• 34:20
  - Yeah, I think. - It was, yeah.
• 34:21
  So they're using this drug,
• 34:22
  so for DLB and they showed some
• 34:25
  cognitive advances and that is great.
• 34:28
  So just said that
• 34:30
  the Reese clinical trials coming out
• 34:32
  for these diseases that is dementia
• 34:33
  with Lewy bodies, but we need more.
• 34:36
  Yeah, so it was really good.
• 34:39
  It was really, really good.
• 34:42
  - Really exciting meeting.
• 34:44
  So we probably should be wrapping up.
• 34:46
  So I'm just thinking,
• 34:48
  was there any particular research area
• 34:50
  that any of you just think,
• 34:52
  you know, is the future
• 34:54
  where this field should be really
• 34:56
  focusing their ideas
• 34:59
  and where think we should all be going next?
• 35:02
  - Big question. - That's a big question.
• 35:04
  - Yeah, yeah.
• 35:05
  I think we all have
• 35:06
  our own preferences and buying.
• 35:07
  - Yeah. - You know, our backgrounds.
• 35:09
  - I think the bio is a very,
• 35:13
  yeah, theme that goes again along
• 35:15
  in many talks, I think yeah,
• 35:18
  understanding, but for just
• 35:20
  a researcher as we are,
• 35:21
  I think just coming to these
• 35:22
  conferences and getting inspired
• 35:24
  on what's moving in the field
• 35:26
  and which models to use
• 35:28
  to be more translatable,
• 35:30
  for example, to the diseases.
• 35:32
  And I've learned a lot on
• 35:34
  which in vivo models also to use
• 35:36
  in the field and they get more and more,
• 35:41
  yeah, specific also to, for example,
• 35:45
  if you have lysosomal dysfunction
• 35:46
  and Parkinson's disease,
• 35:47
  you can actually create a mouse model
• 35:49
  that is linked to a GBA mutation and so on.
• 35:54
  And also just to see that a lot of
• 35:57
  complex cell models also evolving
• 35:59
  and being validated well.
• 36:01
  And I think that's really
• 36:03
  a good way to go in the research field
• 36:05
  to have these complex models
• 36:07
  that really represent the human body
• 36:09
  and the disease the best way.
• 36:12
  - Yeah, yeah, good point, I agree.
• 36:13
  And I suppose, I thought maybe
• 36:17
  you meant in terms of like the theme
• 36:19
  of like where research is mainly going.
• 36:21
  I'd say there was a lot of focus on
• 36:23
  neuroinflammation a few years ago,
• 36:26
  but I'd say, I think because
• 36:28
  of the link between, you know,
• 36:29
  where we talk about metformin
• 36:31
  and how, I think there's a lot
• 36:36
  to speak about when
• 36:37
  it comes to like hormonal changes.
• 36:41
  You know, if you have diabetes,
• 36:43
  all these different other factors
• 36:45
  like epigenetic modifications.
• 36:47
  I just think it's really important
• 36:48
  that it's kind of seen more
• 36:50
  as kind of a whole,
• 36:51
  I know it's easy to really
• 36:53
  hone in on just one particular thing,
• 36:55
  especially when we're researchers
• 36:55
  and we're looking at literally
• 36:57
  like molecular basis, but yeah,
• 37:00
  I think maybe if there's
• 37:02
  more collaboration between clinicians
• 37:03
  and the researchers to kind of have
• 37:05
  more of those discussions,
• 37:06
  I think that would help the way forward.
• 37:09
  - And that reminds us about
• 37:10
  being patient-centered, doesn't it?
• 37:11
  - Yeah. - Because one of the things
• 37:13
  that I've talked about is
• 37:14
  that Alzheimer's disease, for example,
• 37:16
  takes your whole life to develop
• 37:19
  and it's about, you know,
• 37:20
  the experiences and the genetics
• 37:22
  and the environment of the person
• 37:24
  and what leads to that
• 37:25
  outcome and presumably,
• 37:27
  the same for Parkinson's disease.
• 37:28
  So just thinking about
• 37:30
  exactly the hormones and the effects.
• 37:32
  One thing I thought was missing actually,
• 37:35
  which I was a bit surprised about,
• 37:36
  was there was nothing about infection.
• 37:39
  So I think a few years ago,
• 37:40
  there was an idea that if you
• 37:42
  are protected against herpes virus,
• 37:44
  that you would
• 37:46
  have a resilience to Alzheimer's disease.
• 37:48
  And I didn't see anything
• 37:50
  about that this time.
• 37:51
  - I didn't really catch
• 37:52
  anything like that. - No, no.
• 37:53
  - It was quite interesting
• 37:54
  'cause I do think that if you are to get
• 37:58
  a severe infection then, you know,
• 38:00
  it sort of makes sense, doesn't it?
• 38:02
  That it could trigger changes
• 38:03
  and dysfunction, so it's quite
• 38:06
  interesting that that didn't come up.
• 38:08
  - No, that's true
• 38:09
  and that it's actually also
• 38:10
  true with the neuroinflammation.
• 38:11
  I think there's been a lot
• 38:13
  of talks focusing on the lipids
• 38:15
  and the lysosomes especially,
• 38:17
  in both Alzheimer's and Parkinson's.
• 38:21
  (upbeat music)
• 38:26
  - So it's been a really fantastic conversation.
• 38:28
  I've really enjoyed talking to you all.
• 38:31
  And I just wondered if any of you
• 38:34
  presented posters or talks
• 38:35
  at this meeting and whether you
• 38:37
  wanted to say a little bit
• 38:38
  about what you did.
• 38:41
  - You can go. - Oh yeah, yeah.
• 38:43
  I did have a poster.
• 38:45
  I was on the first shift 'cause
• 38:47
  there was two shifts for the whole conference.
• 38:50
  And my poster focused more on
• 38:53
  the cytoplasmic to nuclear translocation
• 38:57
  that I see in dementia with Lewy bodies
• 38:59
  and Alzheimer's disease cases.
• 39:03
  So I am using postmortem brain tissue
• 39:05
  as well as, brain slides
• 39:07
  from the frontal cortex of patients
• 39:09
  from the control cases,
• 39:11
  prodromal Alzheimer's disease
• 39:12
  and dementia with Lewy bodies.
• 39:14
  And specifically, for the postmortem
• 39:16
  brain tissue, what I do is,
• 39:17
  I fractionate the tissue into the nucleus
• 39:19
  and the cytoplasmic fractions.
• 39:21
  And what I saw was really interesting,
• 39:23
  we still don't understand it
• 39:24
  when we're still in the process
• 39:25
  of increasing our end numbers,
• 39:27
  is that we do see there's differences
• 39:29
  in the cytoplasmic
• 39:30
  and the nuclear fractions on dementia,
• 39:33
  sorry, in DNA damage repair proteins
• 39:35
  'cause like I said before,
• 39:36
  I'm interested in the role
• 39:38
  of these proteins and in disease
• 39:43
  and we do see that there is a downregulation
• 39:46
  of this proteins of the Ku70
• 39:48
  and the APEX1 protein
• 39:50
  in the cytoplasmic fraction.
• 39:52
  And there is a potential
• 39:54
  upregulation in the nuclear fraction.
• 39:57
  We're still trying to understand,
• 39:58
  there's a lot of variability especially
• 40:00
  in dementia with Lewy bodies.
• 40:01
  Which brings back to the question
• 40:03
  actually, and these disease dementia
• 40:05
  with Lewy bodies actually might
• 40:06
  not be pure that all these
• 40:08
  co-pathologies that we were talking
• 40:09
  before actually contribute to all
• 40:11
  the changes that we observe
• 40:12
  and this variability that we observe.
• 40:14
  But then I've also used brain tissue sites
• 40:18
  to stain for Ku70 and APEX1 proteins.
• 40:22
  And again, I do see this shift
• 40:24
  from the cytoplasm into
• 40:25
  the nucleus in Alzheimer's disease
• 40:27
  and dementia with Lewy bodies cases,
• 40:29
  which is really striking.
• 40:30
  So then something else that
• 40:35
  I am working on is cellular models.
• 40:36
  So we try to have a shift
• 40:38
  and get a step back to understand
• 40:41
  the mechanism of why
• 40:43
  we're seeing what we're seeing.
• 40:44
  So I am using the SH-SY5Y cells,
• 40:48
  some differentiate in neuron like phenotypes.
• 40:51
  And in order to induce DNA damage,
• 40:53
  I use etoposide,
• 40:54
  which is a top mastocytosis 2 inhibitor
• 40:57
  and something that's really striking.
• 40:59
  And what we observe is that
• 41:01
  when we induce DNA damage using
• 41:03
  this chemotherapeutic drug etoposide,
• 41:08
  I see that there is an increase
• 41:10
  of phosphorylated nucleus in
• 41:12
  with increase in concentrations
• 41:13
  of the drug without any changes
• 41:16
  in the total levels of alpha-synuclein
• 41:18
  and the total levels of tau.
• 41:20
  And I don't see any phosphorylation of tau.
• 41:22
  That's why I really love that talk
• 41:24
  as well 'cause they do see
• 41:25
  like similar things.
• 41:27
  And also, so we're in the process
• 41:30
  of doing further experiments on this
• 41:32
  and like splitting into
• 41:33
  the nuclear cytoplasmic fractions.
• 41:36
  And also, we've also produced
• 41:39
  generated some preformed fibrils
• 41:41
  from alpha-synuclein using
• 41:43
  the Michael J. Fox Foundation protocol.
• 41:46
  And we wanna use these preexisting
• 41:48
  pathology, the preformed fibrils
• 41:50
  with and without the DNA damage
• 41:52
  inducing agent atococyte
• 41:54
  to see what comes first.
• 41:56
  So try and understand basically,
• 41:57
  the basics behind what we see.
• 42:01
  Yeah, so it's an exciting work.
• 42:03
  But yeah, that is all me.
• 42:05
  That's what my poster was about.
• 42:06
  - Well, that sounds really interesting.
• 42:08
  So I really look forward to
• 42:09
  hearing what happens in the end.
• 42:11
  - Thank you very much.
• 42:12
  Yeah, yeah. - [Prof Louise] So exciting.
• 42:13
  - Thank you.
• 42:14
  - [Prof Louise] What about you, Lauren?
• 42:15
  - So I also had a poster.
• 42:17
  So I actually have only recently
• 42:18
  started my postdoctoral position
• 42:20
  at the University of Dundee,
• 42:21
  but I have my finalised work
• 42:24
  for my PhD at Newcastle University.
• 42:27
  So that's what I presented in the poster.
• 42:29
  So what I've shown using
• 42:31
  a transgenic mouse model
• 42:32
  of ultrasound endocrinopathies,
• 42:34
  A30P mouse, I looked at
• 42:36
  a presymptomatic age range
• 42:37
  between two and four months.
• 42:38
  And I specifically wanted to look
• 42:40
  at the hippocampus
• 42:42
  and the hippocampal neurons.
• 42:44
  And it was actually kind of like
• 42:46
  an accident as to how I found this
• 42:48
  is when I zoomed in on the images
• 42:49
  and the parietal layer,
• 42:50
  I saw that there was kind of
• 42:51
  differential expression of
• 42:52
  alpha-synuclein in the A30P mouse
• 42:55
  between cells of the same mouse.
• 42:56
  And I thought it was quite strange.
• 42:58
  I did a frequency distribution
• 42:59
  and I categorise these cells
• 43:01
  that are having low, medium,
• 43:03
  high levels of alpha-synuclein.
• 43:04
  And I went to look at how the mitochondrial
• 43:09
  respiratory chain subunits
• 43:10
  are impacted when there is either
• 43:11
  low, medium or high levels of alpha-synuclein.
• 43:13
  And interestingly, we found that
• 43:15
  in the cells that had the very
• 43:16
  high levels of alpha-synuclein,
• 43:17
  there was a significant increase
• 43:19
  in mitochondrial complex one subunit
• 43:21
  and also, mitochondrial complex four.
• 43:23
  Which is interesting because
• 43:24
  from what Sarah Berman shown in
• 43:27
  patient data that there
• 43:28
  was actually initial increase.
• 43:30
  So I thought it kind of linked very nicely,
• 43:33
  I know that I was using a mouse model,
• 43:35
  but it's reassuring that, you know,
• 43:37
  it's actually seen in some patient data
• 43:39
  as well that it might be a commonality of
• 43:42
  this compensatory response initially.
• 43:45
  - That's what conferences
• 43:46
  are for really, isn't it,
• 43:47
  when you really get some sort of
• 43:49
  backup on what you think
• 43:50
  and then you start thinking about
• 43:53
  how that compares to other people.
• 43:54
  That sounds fantastic. - Yeah.
• 43:56
  - Really exciting stuff. - Thanks.
• 43:59
  - What about you, Sofie? - Yes, yes.
• 44:00
  So I- - You gave a talk
• 44:02
  for a YouTube video. - Yes, that's true, yes.
• 44:06
  So I did present a poster as well.
• 44:11
  And that was for Vesper Bio,
• 44:12
  which I just mentioned before.
• 44:13
  We developed small molecules,
• 44:15
  sortilin inhibitors,
• 44:17
  and we actually have one called,
• 44:19
  (indistinct) which has just finalised
• 44:21
  or completed a Phase 1b/2a trial.
• 44:24
  And we have a talk later today
• 44:27
  on the safety and the efficacy of that.
• 44:29
  And I can spoil alert, it's good.
• 44:33
  But I did present
• 44:34
  more the preclinical stuff.
• 44:36
  So as I mentioned, we increase
• 44:38
  by blocking the sortilin receptor,
• 44:40
  we increase the very important
• 44:42
  progranulin protein in the brain.
• 44:44
  And we do it both extracellularly,
• 44:45
  but also intracellularly.
• 44:47
  So by that, we improve the lysosomal
• 44:49
  function, it's neuroprotective,
• 44:52
  but also, anti-inflammatory.
• 44:54
  So that's very good.
• 44:56
  And then I talked a lot about
• 44:58
  the potential we have in Parkinson's
• 44:59
  disease because that we
• 45:01
  are in a very preclinical stage.
• 45:04
  And that's especially with
• 45:05
  the DAF complex I mentioned before.
• 45:07
  So the sortilin p75 DAF complex,
• 45:10
  which especially is on
• 45:11
  the dopaminergic neurons in
• 45:13
  the substantia nigra pars compacta.
• 45:15
  So very important
• 45:16
  for Parkinson's disease patients.
• 45:18
  So when we block that,
• 45:19
  we increase the cell survival.
• 45:21
  And right now,
• 45:22
  we're in a very beginning stage.
• 45:24
  So we've actually tried with
• 45:26
  the AV, the viral alpha-synuclein mouse model.
• 45:30
  Unfortunately, it was a very harsh model.
• 45:33
  So we saw 90% loss of
• 45:36
  the dopaminergic cells, which is a lot.
• 45:39
  So unfortunately, we couldn't really
• 45:41
  rescue anything that wasn't there.
• 45:44
  So I mean, we've also really
• 45:46
  learned a lot from this conference
• 45:48
  and got a lot of good feedback
• 45:50
  on what the next steps are.
• 45:51
  And we are very lucky to have
• 45:53
  a funding from the Michael J. Fox
• 45:55
  as well, which are really incredible
• 45:57
  to work with and have also
• 45:59
  had a lot of good talks with them
• 46:00
  here at at the conference.
• 46:03
  (upbeat music)
• 46:08
  - So that brings us to
• 46:10
  the end of our ADPD Conference,
• 46:12
  reflections from Copenhagen.
• 46:14
  Thank you all so much for
• 46:15
  your fantastic input and discussion.
• 46:18
  I really enjoyed it.
• 46:18
  I hope you did too.
• 46:20
  Good luck on going home,
• 46:23
  although, don't have to go far.
• 46:25
  - Not so far.
• 46:27
  - If you want to learn more about
• 46:29
  the research we discussed today,
• 46:30
  you can find links and further
• 46:32
  information in the show notes.
• 46:34
  On our YouTube channel,
• 46:36
  you'll find many of the posters short recordings.
• 46:38
  I've listened to them and watched them
• 46:39
  and they are really fantastic.
• 46:41
  I'm so impressed with the way
• 46:42
  that people are able to communicate
• 46:44
  their research as you've seen today.
• 46:47
  So the researchers will share
• 46:48
  short summaries of their work
• 46:50
  presented at the conference.
• 46:52
  But for now, I'm Professor Louise Serpell
• 46:55
  and you've been listening
• 46:56
  to the Dementia Researcher Podcast.
• 46:59
  Goodbye. - Bye.
• 47:01
  (upbeat music)
• 47:02
  - [Voice Over] The Dementia Researcher
• 47:03
  Podcast was brought to you
• 47:04
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• 47:06
  with generous funding
• 47:07
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• 47:09
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• 47:10
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• 47:12
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• 47:13
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• 47:15
  and Race Against Dementia.
• 47:17
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• 47:18
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• 47:20
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• 47:22
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