January 27, 2025 • 31 mins
Unlock the secrets of the brain's most enigmatic conditions with Dr. Mauro Montalbano, our esteemed guest from the University of Texas Medical Branch. He takes us on a journey through his lab's cutting-edge research into neurodegenerative diseases like Alzheimer's, Parkinson's, and ALS. You'll gain a deep understanding of the sinister role played by protein aggregates, particularly amyloid beta and tau proteins, and their prion-like behavior that drives the progression of Alzheimer's disease. Dr. Montalbano's journey from Sicily to Galveston adds a personal touch to his pioneering efforts in neuroscience, underscoring the critical need to decipher early-stage processes in disease progression.
Our discussion ventures into the unpredictable realm of Alzheimer's, illustrated by a compelling family story that highlights the disease's capricious nature. Despite shared genetics and lifestyle, one sister succumbs to Alzheimer's while the other lives a long life, challenging our understanding of its onset. We examine the ongoing focus on amyloid plaques and the vital roles of microglia and astrocytes in regulating protein buildup in the brain. The conversation also taps into the mysteries of cognitive resilience among certain individuals and how current therapies aim to reduce inflammation as a strategy to slow progression.
We further explore the intricate link between vascular health and Alzheimer's, where factors like atherosclerosis, sleep quality, and auditory health are potential culprits of cognitive decline. Dr. Montalbano guides us through the complexities of treating late-stage Alzheimer's and the promise of early intervention and preventative strategies. In a world increasingly focused on personalized medicine, he sheds light on the challenges and potential breakthroughs on the horizon, while also pondering the possible long-term impacts of COVID-19 on dementia prevalence. This episode promises to enlighten and challenge your understanding of these profound neurological puzzles.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 2 (00:09):
This is a podcast about One Health the idea that
the health of humans, animals,plants and the environment that
we all share are intrinsicallylinked.
Coming to you from theUniversity of Texas Medical
Branch and the GalvestonNational Laboratory, this is
Infectious Science, whereenthusiasm for science is
contagious.
Speaker 3 (00:28):
So today we have a special guest here in our
podcast, dr Mauro Montalbano.
I'm trying to say that with mybest Italian accent, which is
non-existent.
He's an assistant professorhere at UTMB and then at the
neuroscience department, andwe'll hear some really exciting
work that they are doing in thatdepartment, and he will also
(00:50):
tell us a little bit about theconnection to some of the
amyloid buildup in the brain inform of dementia, and so we're
very excited to have him here.
So what are we going to ask him?
Speaker 2 (00:59):
Yeah, so tell us a little bit about your lab's
current work.
Speaker 4 (01:03):
Okay, so first of all , thank you for having me here.
It's a pleasure.
I actually hear some of yourpodcast.
That's super cool to be here.
Great, we have listeners.
Speaker 3 (01:15):
We have listeners on the show your.
Speaker 4 (01:17):
Italian is perfect.
So that is 10 out of 10 for mylast name.
Yeah, so a brief description ofwho I am.
So I'm assistant professor atthe Mitchell Center for
Neurodegenerative Disease atUTMB.
So my lab work mainly to studyhow protein aggregates within
(01:37):
the human brain, in particularin Alzheimer's disease, but we
cover other neurodegenerativediseases like Parkinson's
disease, frontal temporaldementia and amyotrophic lateral
sclerosis as well.
So our vision is to find a wayto basically slow down or
completely block the buildup ofthis protein aggregation within
(02:00):
the human brain in aging process.
Basically, Perfect.
Speaker 1 (02:03):
So, now that you've given us a little bit of
background on your work and yourlab, can you give us a little
bit of background on yourself?
Speaker 4 (02:10):
So about me?
Okay, he's the best soccerplayer that we have on YouTube.
Yeah, rather than that, I'm alittle bit out of shape, but
anyway.
Yeah, basically, I'm Italian,so I come from Palermo, sicily.
Speaker 3 (02:29):
Is this really Italian, though, like Sicily, is
always like its own littleItaly isn't it?
Speaker 4 (02:33):
Yeah, exactly, we consider ourselves before
Sicilian and then Italian.
Speaker 2 (02:37):
It's like Texans before Americans, oh really.
Speaker 4 (02:40):
Oh, wow, that's cool.
Yeah, it's beautiful, so don'task me why I end up in Galveston
.
Speaker 2 (02:48):
It's a downgrade yeah exactly.
Speaker 4 (02:51):
But yeah, basically my background is I got my
bachelor in biological science,then my master in molecular and
cellular biology at Universityof Palermo and then for
basically an internationalprogram between University of
Palermo and UTMB.
I ended up as a PhD student andI work in surgery department
(03:15):
studying hepatocellularcarcinoma.
So my background was mostlycancer biology.
But then after that Idiscovered the neuroscience
during my postdoc First postdoc,actually, always here under the
mentorship of Dr Modamedi,studying the amyloid formation
in the retina of patients withAlzheimer's disease Interesting.
(03:38):
And then I joined Dr Cayet'slab in the Mitchell Center to
study in deep the formation andthe buildup of these protein
aggregates.
Side effect of that is that weare not only studying the
protein aggregation but inparticular we are focused also
in gene expression.
So we are giving another pointof view of the typical vision of
(04:00):
protein aggregates inneurodegenerative diseases.
Speaker 2 (04:03):
And when you talk about protein aggregates, are we
always referring to those aslike prions, and are they a
natural part of the agingprocess for humans?
Speaker 4 (04:12):
So this is a really good question.
I would like to answer that,say that it's under
investigation.
Still, we know exactly whichare the two major factors that
during the pathogenesis ofAlzheimer's in particular, two
proteins are involved on thatand they are considered quite
officially pre-like protein ThenI will spend a little bit more
(04:36):
time on the terminology and theyare the amyloid beta and tau.
These are the two major factors, so they act as a prion.
This is well studied, wellrecognized, but there is still a
strong debate in the field toconsider it completely fully
prion protein.
(04:56):
So we know, for example, thatif you have neurons, for example
, in culture in the lab, youexpose them to this prion-like
protein, the endogenous protein.
So the endogenous amyloids,endogenous tau.
They start to misfold and thenaggregate.
It's like exactly the prionprotein, exactly the same
(05:19):
principle, but still the fieldis preferred to put a dislike on
the side, because the questionis okay, but if you, for example
, get in contact with those, youwill develop the disease.
This is not what happenedactually, or there are no
evidence on this, like for theprion disease itself, right, but
the principle of spreading orthe formation of the first
(05:43):
aggregates is exactly the sameprinciple.
So you have a beautiful protein.
They do their function for somereason that we still don't know
.
A certain point during ouraging process they misfold, they
acquire the not properstructure and they spread up
this kind of toxic structure toother protein.
(06:04):
Let's say, for example, for tau.
Tau is a very nice protein.
It usually binds a tinystructure within our cells
called microtubules.
These are tubules that keep upwith the cells and maintain
their shape.
So if this tau protein misfolds, basically the cells start to
(06:25):
have some problem and this tau,misfolded tau transmits to the
other tau protein the misfoldedshape.
They start to basically do notfunction properly.
They start to aggregate, theystart to accumulate and later on
these determine the death ofthe cells, in this case of the
(06:46):
neuron, and that's the neuronare not replicative cells.
So when we lost a neuron welost forever.
But think about the crazythings is that this happened in
a very big time lapse for thehumans.
People can with the disease for20 years, 15, 20, 20 years.
So it's a very slow process.
(07:07):
This is why many labs now focuson the early onset of the
disease, when the tau or theamyloid start to form what we
call prionic oligomers.
Speaker 3 (07:23):
So cool.
I have so many questions.
I think every five questionsjust popped into my mind.
Yeah, I'm just kind of somerapid fire for me.
So do you know if animals havealzheimer's disease, or do you
have something comparable in theanimal kingdom?
Speaker 4 (07:37):
so I will answer you with a maybe no means.
I'll'll explain.
I'll explain sopathological-wise.
No animals really develop whathuman develops in terms of
pathology.
There is some study that showup that something that is
(08:00):
comparable to the humanpathology happen in some species
of monkey, and I guess they'recalled marmoset, as I recall.
They're a small monkey, butother animals do not develop
what humans develop.
This could be to the fact thathumans age much longer than
(08:21):
others.
And other animals age naturally,but our aging process is very
how I can say it's been improvedstrongly.
If you think, 100 years ago theaverage of our age wasn't the
one that we have today.
So in a century or in twocenturies we basically doubled
(08:46):
the expense of our life.
So this presented a newchallenge for the neuronal
biology or the brain biologyitself.
This is valid also for otherorgans.
Speaker 3 (08:55):
So my cat just turned 19 and I think she has
Alzheimer's disease.
Sometimes she forgets wherestuff is, so maybe I have this
possibility to challenge thedogma right.
Speaker 2 (09:08):
How many cats live till 19, though she's got a vet
for a dad.
Speaker 1 (09:12):
That's why she's like that's fair, Although I bet if
you put her in an MRI you mightsee other stuff that you.
Speaker 4 (09:18):
Going back to your question, for example, we use
mice as a model.
Mice do not develop naturallyright alzheimer's, so we have to
create a transgenic mice thatbasically reproduce what we
found out.
And this is the reason also why, unfortunately, many clinical
trials do not work out in human.
(09:39):
Because they work perfectlymice, we clean the mice brain
perfectly.
There is a colleague that tomake fun about it, to say we can
cure Alzheimer's in mice.
So this tells you how much iscomplex Study this kind of
disease in animal models likemice, for example.
Speaker 3 (09:58):
Yeah, but the lifespan of a mouse is only two
years, right.
Speaker 4 (10:01):
But they have so many other properties that make
their brain very resilient tothe prion spreading and
aggregation itself, because theypossess, for example, a very
reactive inflammatory responsecompared to the human.
We think right now, in the lastyears, that now inflammation in
(10:22):
the brain play a crucial rolefor the buildup and the early
manifestation of this proteinaggregate.
Speaker 2 (10:29):
So that's what I was going to ask what is driving
that sort of original kind ofmisfolding?
Is it a traumatic brain injury?
Is it inflammation?
Is it like potentially toxicityfrom?
Speaker 4 (10:40):
something.
If I have the answer for thisquestion, I'm not maybe here,
I'm in Sweden receiving theNobel Prize.
So that's a great question, no,look, I report every time an
example I had in my family sideof my grandma and auntie
basically, and she died withAlzheimer's disease.
(11:01):
And this auntie lives in afamily of nine.
There are seven brothers, myauntie and my grandma.
So she developed Alzheimer's onher 60 around.
I love her, it was like asecond grandma for me and she
developed the Alzheimer's.
And my grandma two days ago did99 years old she just made her
(11:23):
birthday and they were sisters.
So the reason lies downprobably to many factors.
These diseases aremultifactorial diseases.
For the last 20 years peoplefocus just on amyloids.
Right, it's the amyloids, theplaques.
We have to block this stuff andwe will cure the disease.
We have to block this stuff andwe will cure the disease.
(11:45):
After 20 years the FDA approvedjust two antibodies for amyloid
and the process is very slow.
But the example of my grandmais just to tell you that they
live in the same family, theyhave the same kind of education,
they have basically also acomparable genetic background.
(12:05):
They were both sisters and onedeveloped Alzheimer's and one
make 99 years.
Speaker 1 (12:11):
And I would assume they both lived a fairly similar
lifestyle as well.
Exactly Similar lifestyle,similar diet similar physical
activity.
Speaker 4 (12:19):
No, physical activity because at the time there were
no gym or they should take carejust of the family.
Very low also education One ofthe risk factors for Alzheimer's
, for example, has beenestablished that low education,
for example.
So if you keep your brain lowwith low activity, so you read
or you do exercise or all thosebrain games that are cool things
(12:40):
that keep up with andcounteract actually the build-up
of this protein.
But the truth is that is amultifactorial thing.
Multifactorial thing and thisbring complexity we we would
like to make in the past easier.
Because you find out prionaggregation.
They usually in the brain formsat the beginning in a very
(13:01):
specific brain region that iscalled the hippocampus and
entorhinal cortex.
This is the region thatgenerally people associate with
the memory.
In fact memory is one of thecognitive dysfunction that
usually people develop inAlzheimer's.
But then what happens is like aprion, once the neurons die, or
through the inflammatory system.
(13:23):
Once the neurons die or throughthe inflammatory system, so
they are called in the brainmicroglia and astrocytic cells,
astrocytes.
So basically it looks likethese cells are not able anymore
to manage the cleanup thatusually occur in our brain
during aging and they alsomediate the spreading across all
the other regions of our brain,the spreading across all the
(13:45):
other regions of our brain, andgradually they bring dysfunction
in many cognitive aspects ofour life.
Speaker 1 (13:51):
So the astrocytes and the microglia assist in the
spreading of these misfoldedproteins.
Speaker 4 (13:56):
Initially they assist to clean up, but at a certain
point, when the system isoverwhelmed, there are theories
that actually make it faster orthere is a strong debate still
on that.
It's very fascinating.
But the job basically is toclean up the microglia.
For example, take care of oursynapses and the synapses are
(14:16):
those portions that connect oneneuron to another neuron and
make us functioning for all ourcognitive or physical activity.
And actually when theseamyloids forms at the beginning
of the disease, the synapsesthat looks like are the most
sensitive parts of our neuronand they burn and microglia
usually come close to thosesynapses that are damaged and
(14:38):
they start to eat.
Clean up all those surroundings,try to keep the neuron as much
as possible functional.
But when you have anoverwhelming amyloid formation
when I say amyloid I includealso the tau protein, the other
component they start to get,let's say they're not able to
manage it anymore and theyacquire some of them.
(15:01):
There is like a beautifulpapers published on it.
Some of these microglia startto became what they call disease
associated microglia, so makethe prion spreading even faster.
Interesting, in fact, in peoplethat have a very fast, I'd say,
first development of thedisease, they have a very strong
microglial activity Interesting, so it's very interesting.
(15:24):
But also the aspects that wehave to consider are so many
that we need to go step by stepon each factor.
Speaker 3 (15:31):
So just to recap, so you were saying with the
microglia, so they normally comein, they clean up, right, and
what I know about prion diseasesis that they accumulate within
the cell and then the cellcannot get rid of them.
So what are you saying is themicroglia come in, they pick up
the disease or the particles ofthe cell that was diseased, and
then they move to a differentplace and they carry the
(15:54):
amyloids with them to adifferent place.
Is that what you're?
Speaker 4 (15:57):
saying yeah, that is one of the mechanisms.
The other mechanism is thatthis transmission happens neuron
by neuron, for example throughthe synapses themselves or
through the secretion ofexosomes or other microvesicles.
Think about that.
This process, as I say, happenslong in time.
Okay, it takes a while.
(16:18):
So our neurons do not dieimmediately, so they have a
certain capacity to rearrange.
Another theory is that, anyway,we form some sort of aggregates
, even in normal aging.
There are cases of people thathave the pathology, for example,
but they do not show anycognitive symptoms or cognitive
(16:39):
impairments.
So there is a system, for sure,that is able to manage even the
presence of the prion andamyloids, the plaques, the
tangles of tau and whatever.
But maybe these people have astronger process that is able to
manage it and the cognitivefunction are still integrated.
(16:59):
But, as to recall, this isalways on the synapses.
But the synapses are verysensitive cellular portion to
the prions because they've beenbinded and then this should work
as a signal for the microglia.
So, okay, this synapses is notproperly working, I'll engulf, I
heat it and then I willdegradate.
But again, which is themicroenvironment around, how the
(17:24):
other, also the astrocytes, areworking up on this.
So this is still underinvestigation and I guess many
new tools and also for thetherapy actually is focusing on
keeping an inflammatory statevery low.
So that is another possibletherapeutic intervention.
Speaker 1 (17:45):
I was going to ask do you know the role that, like
circulation and like good orimproved circulation,
potentially plays in thedevelopment and the progression
of Alzheimer's?
Because I know with otherneurodegenerative diseases
vascularization throughout thebody plays a really big role,
like in maintaining theintegrity of neurons and the
myelin sheaths and stuff likethat.
(18:05):
So is there like a well-knownrole that vascularization plays
in Alzheimer's?
Speaker 4 (18:10):
Yeah, this is a great question.
So there are a study and it'swell-established also that
exists a form of vascularamyloidosis it's called, where
basically the amyloids not onlyform in neurons but form also
and form plaques within theblood vessels.
Now where this comes from theneurons, or is it just the
(18:33):
endothelial cells, for example?
I don't know, but it'srecognized.
It's called CAA cerebralvascular amyloidosis and this is
quite a form that you can findin Alzheimer's as well in
Alzheimer's patients, but notall Alzheimer's patients develop
the deposition of amyloids,because there is also the
possibility that your brain isoverwhelmed with these amyloids.
(18:56):
The spreading is on, andanother way that maybe our body
has to clean up is to flush outthese amyloids through the
vessel.
But again, how much amyloid weare talking about is not just
amyloid, beta, it's tau, Maybeit's even other proteins.
Speaker 3 (19:14):
I like Christina's question, I want to ask
basically from a different angle.
Speaker 2 (19:18):
So we live in a society where so many of us
suffer of bad vascular health,right, atherosclerosis,
hypertension, hypertension andstuff like that and
atherosclerosis for listeners isessentially your blood vessels
are getting clogged, and it isvery common in America and all
over the world.
Speaker 3 (19:37):
Absolutely yes, and thank you for clarifying that.
So is there a correlationbetween bad blood flow to the
brain, or atherosclerosis, andAlzheimer's disease?
It's definitely a risk factor.
Speaker 4 (19:49):
It's definitely a risk factor, but even the
sleeping has been found has animpact on the development of
alzheimer's or form of dementia.
So little sleep is risk factoryeah, I don't know what that
means with bad sleeping, butlike an interrupted sleep or I'm
(20:11):
not an expert on sleeping, butI know that sleeping is playing
a crucial role.
I'm an expert on sleeping.
Another association has beendone with auditory system, and
if you have issues also withyour ear, really yeah, because
that does not stimulate certainparts of your brain and make
(20:31):
your neuron maybe evenvulnerable.
I don't know exactly themechanism, but many aspects of
our lifestyle impact the workingprocess of the brain.
So basically the principleright now, because there is no
cure for this disease, so, likefor other diseases, have a good
lifestyle, eating well.
(20:53):
But this is valid in generalfor any kind of disease, for
cancer, for cardiovasculardiseases and even for dementia.
But again, we discussed beforethe low study or like low
education didn't work out for mygrandma.
She reached 99 years oldwithout any form of dementia.
(21:13):
But again we still need to digmore on the cause.
Maybe we are just seeing theeffects.
Like the amyloid and the prionthemselves is a strong event.
That happened at the beginning.
But we still don't know exactlywhat they are inducing as well.
Human brain is so complex, veryhard to study, so it's very
(21:35):
challenging for me as ascientist in the field exciting
to study.
Speaker 3 (21:42):
So, mauro, I want to come back to your point of the
sleep quality that you refer to,that sleep has an influence on
this.
So there's a new class ofsleeping aids that have been
released now.
Right, we used to have the GABAreceptor-based ones, and
there's now this new class thatbasically reduces your
(22:02):
wakefulness, and I saw there wasan article that speculated on
that.
It actually can help reduceAlzheimer's, and I don't know
what the mechanism is or how itwould avoid accumulation of
amyloid.
Do you think that's a crazyidea?
Have you seen those reportsthat this could?
Speaker 4 (22:20):
be a treatment.
I didn't see those reports, butmaybe it will detect some
impact somehow.
But I don't know.
Honestly, it's hard to say that.
Maybe the other problem is tosee an effect on the incidence
of some therapy or something.
Anyway, you need a larger timewindow.
Maybe this study will, or thetreatment of a particular
(22:42):
compound or something that weregularly use.
The correlation will be foundin 10, 20 years since it's been
developed found in 10, 20 yearssince has been developed.
Speaker 2 (22:56):
So my question with this is I think that there's
always this strong interest incuring in a lot of like
pharmacology stuff, but what youdescribed earlier is that
people can have the pathology ofthis in the brain but not have
symptoms, and so we coexist withthis, or some people can
coexist with this right, Justlike we might have staph on our
skin, but it's not a problem,unless we have a severely deep
cut and then it's in our generalsystem.
Potentially, plaques aren't theproblem if they're not becoming
(23:19):
widespread and your body cankeep up on managing them, right?
So is the interest then inpreventing, like in the field of
Alzheimer's research?
Is the interest in preventingthe plaques from forming at all
or in finding a way to help thebody continue to manage the
plaques that might be formingjust naturally?
Speaker 4 (23:38):
Yeah, that's great.
So the approach at thebeginning, many years ago.
This is why we, the FDA,approved two antibodies right
now available for the amyloidplaques, because many years ago,
with the study of the plaques,scientists say, okay, this is a
difference between an Alzheimercase and a person that do not
(24:01):
have.
So if we maybe we block or wedegraded these plaques, we can
cure the disease.
But again, was not this thecase?
Okay, so imagine also that whenpeople develop plaques or this
is the very final stage.
So to me as a scientist on thefield, it's hard to think about
a cure for late stage.
(24:23):
It's almost impossible becauseat this stage, basically, the
patient already lost.
It's not just the loss ofneurons, but it's the loss of
the connections.
Remember our memories.
Our task has been made by anintricate system that we still
don't know exactly how to workit out.
So when you burn out or youlost that neurons, you could
(24:48):
lose forever those memories.
So thinking about a cure in latestage, I don't think even is
convenient.
So this is why our labs in theMitchell Center, for example, we
are more focused on the earlyphase, where those prions start
to form and they are still smalland toxic, yes, but maybe
(25:09):
targetable in terms of therapy.
And the other is the prevention.
So there are many groups thatare working to identify people
that are vulnerable to thebuildup of these protein
aggregates.
That would be cool.
Maybe we can produce in thenear future a vaccine, a kind of
a vaccine that can prevent, forthose that are more at risk, to
(25:33):
develop dementia.
So that is where the field isgoing using immunotherapy, so
antibody, or, as in our case,starting to use genetic therapy,
so a genetic approachInteresting.
Speaker 2 (25:48):
Could you also clarify the difference between
Alzheimer's and dementia,because I feel like in the
public space, people often usethem in a way that's
interchangeable, but they're notright?
Speaker 4 (25:59):
Yeah, no, they're not .
But with dementia we identifyall those kinds of brain
pathologies that basicallyimpair the brain functionality
at different age.
Okay, because, again,alzheimer's, usually the first
symptoms start around 65 and canlast for longer.
(26:19):
But there are other forms ofdementia, like frontotemporal
dementia, that can develop evenbefore in age.
Okay, so, and that is due to abuildup of other protein.
In this case one of the mostimportant is TDP43, is another
amyloid protein.
So maybe we have to deal evenwith more loidogenic, so
(26:40):
prion-like protein, so that thepicture is more complex.
The Alzheimer's disease in thelast years we are starting to
differentiate also maybe theAlzheimer's disease because
there is an historically,naturally I would like to say
chain, because this isassociated with who discovered
the disease, observed for thefirst time, even within that,
(27:02):
what we call Alzheimer's disease.
We have to differentiate thisform.
But yeah, with form of dementia, we always put Alzheimer's and
many others forms of dementiaand remember these are always
progressive.
So in this umbrella of dementiawe always put Alzheimer's and
many other forms of dementia andremember these are always
progressive.
So in this umbrella of dementia, the disease has to be
progressive.
It's not something that has avery short outcome.
It's long in time, more or less, but it happens in years, and
(27:25):
that has to affect the brain, sothe neurons directly.
Speaker 2 (27:28):
So they're always progressive, but there's no way
to predict how quickly it willprogress for any individual.
Speaker 4 (27:33):
This is also about our genetic background.
This is why we are focusing onthe vulnerability of people.
We are not anymore focused juston those protein aspects.
We have to see our background.
It's like also for many othertype of disease where you could.
Why, for example, people thatmade the same chemotherapy for
(27:54):
the same cancer, someonesurvived, someone not.
There is always a context wherewe have to move and that
context is a personal context, agenetic context.
So there is something thatpotentiates our response and we
can live great with plaques,maybe, like those cases.
And there are contexts whereyour genetics or your
(28:15):
inflammation, your again, thecerebrovascular system is not
working properly for somegenetic reason.
Speaker 3 (28:24):
But, mauro, how far away are we from this
personalized medicine that youtalk about?
Because I think we always hearthat personalized medicine is
the thing of the future.
But I remember, for example, Idid 23andMe this genetic test a
long time ago, right, and I haveone of the, the ApoEG alleles
for early onset Alzheimer'sdisease, but it's just a
(28:46):
slightly increased risk but what?
you were saying is this ismultifaceted, right, it depends
on my sleep and then how I takecare of my body, and so on.
So it feels like we're stilllike in the childhood, in the
baby days of personalizedmedicine.
When it comes to dementia, theresearch is all right.
Speaker 4 (29:04):
Yeah, I agree with you, Big progress has been done
in terms of a variety ofpossible therapeutic
intervention.
In terms of variety of possibletherapeutic intervention.
In Dr Kaya's lab, actually, wedevelop an immunotherapy for tau
, not for amyloid that worksperfectly nice.
So hopefully we will test itout in humans as well, with some
(29:24):
clinical trials.
But again, this is a generaltherapy, so it's something that
you apply for everyone.
As you say, I've been heardabout like personal therapy,
even in cancer now 10 years ago,but even there has been like
very challenging as well.
So I guess that for this typeof disease, find a common
(29:46):
mechanism or mechanism-basedtherapy will be a winning card,
or mechanism-based therapy willbe a winning card.
But in terms of years, I thinkthat maybe we will see some
significant impact on the newtherapies within five, ten years
.
Maybe that's the window that Iexpect, looking about the
progress that others are doingwith several types of therapies.
(30:09):
But it's very challenging andagain, and this is why I'm
focused more on the biology westill move our vision a little
bit, I don't want to say faraway from the prion or from the
protein aggregates, but also onthe genetic aspect and how the
genes answer to these proteinaggregates.
(30:30):
Because, maybe the proteinaggregates is not just the cause
, it's just the input to acascade of things that then
determine the death of theneurons in our brain.
Speaker 2 (30:40):
Speaking of inputs that can cause cascades, I
wanted to get your opinion on ifyou think we'll see an increase
in Alzheimer's in ourpopulation because we've had
COVID, which is a neuroinvasivevirus, so it can infect the
brain and COVID can act like atraumatic brain injury right,
and it could certainly causeinflammation.
Do you think we'll see anincrease in Alzheimer's like 20,
(31:03):
40, 60 years down the line?
Speaker 4 (31:04):
I don't know if we will see that increase.
We need to wait a little bit.
Covid happened a few years ago.
Okay, as I say, this diseaseparticular, alzheimer's requires
several years, but there arebeautiful studies that talk
about how a previous infectionfrom other viruses or even
bacteria in the brain can bringvulnerability for the developing
(31:28):
of dementia.
This is a podcast about One Health the idea that
the health of humans, animals,plants and the environment that
we all share are intrinsicallylinked.
Coming to you from theUniversity of Texas Medical
Branch and the GalvestonNational Laboratory, this is
Infectious Science, whereenthusiasm for science is
contagious.
Speaker 3 (00:28):
So today we have a special guest here in our
podcast, dr Mauro Montalbano.
I'm trying to say that with mybest Italian accent, which is
non-existent.
He's an assistant professorhere at UTMB and then at the
neuroscience department, andwe'll hear some really exciting
work that they are doing in thatdepartment, and he will also
(00:50):
tell us a little bit about theconnection to some of the
amyloid buildup in the brain inform of dementia, and so we're
very excited to have him here.
So what are we going to ask him?
Speaker 2 (00:59):
Yeah, so tell us a little bit about your lab's
current work.
Speaker 4 (01:03):
Okay, so first of all , thank you for having me here.
It's a pleasure.
I actually hear some of yourpodcast.
That's super cool to be here.
Great, we have listeners.
Speaker 3 (01:15):
We have listeners on the show your.
Speaker 4 (01:17):
Italian is perfect.
So that is 10 out of 10 for mylast name.
Yeah, so a brief description ofwho I am.
So I'm assistant professor atthe Mitchell Center for
Neurodegenerative Disease atUTMB.
So my lab work mainly to studyhow protein aggregates within
(01:37):
the human brain, in particularin Alzheimer's disease, but we
cover other neurodegenerativediseases like Parkinson's
disease, frontal temporaldementia and amyotrophic lateral
sclerosis as well.
So our vision is to find a wayto basically slow down or
completely block the buildup ofthis protein aggregation within
(02:00):
the human brain in aging process.
Basically, Perfect.
Speaker 1 (02:03):
So, now that you've given us a little bit of
background on your work and yourlab, can you give us a little
bit of background on yourself?
Speaker 4 (02:10):
So about me?
Okay, he's the best soccerplayer that we have on YouTube.
Yeah, rather than that, I'm alittle bit out of shape, but
anyway.
Yeah, basically, I'm Italian,so I come from Palermo, sicily.
Speaker 3 (02:29):
Is this really Italian, though, like Sicily, is
always like its own littleItaly isn't it?
Speaker 4 (02:33):
Yeah, exactly, we consider ourselves before
Sicilian and then Italian.
Speaker 2 (02:37):
It's like Texans before Americans, oh really.
Speaker 4 (02:40):
Oh, wow, that's cool.
Yeah, it's beautiful, so don'task me why I end up in Galveston
.
Speaker 2 (02:48):
It's a downgrade yeah exactly.
Speaker 4 (02:51):
But yeah, basically my background is I got my
bachelor in biological science,then my master in molecular and
cellular biology at Universityof Palermo and then for
basically an internationalprogram between University of
Palermo and UTMB.
I ended up as a PhD student andI work in surgery department
(03:15):
studying hepatocellularcarcinoma.
So my background was mostlycancer biology.
But then after that Idiscovered the neuroscience
during my postdoc First postdoc,actually, always here under the
mentorship of Dr Modamedi,studying the amyloid formation
in the retina of patients withAlzheimer's disease Interesting.
(03:38):
And then I joined Dr Cayet'slab in the Mitchell Center to
study in deep the formation andthe buildup of these protein
aggregates.
Side effect of that is that weare not only studying the
protein aggregation but inparticular we are focused also
in gene expression.
So we are giving another pointof view of the typical vision of
(04:00):
protein aggregates inneurodegenerative diseases.
Speaker 2 (04:03):
And when you talk about protein aggregates, are we
always referring to those aslike prions, and are they a
natural part of the agingprocess for humans?
Speaker 4 (04:12):
So this is a really good question.
I would like to answer that,say that it's under
investigation.
Still, we know exactly whichare the two major factors that
during the pathogenesis ofAlzheimer's in particular, two
proteins are involved on thatand they are considered quite
officially pre-like protein ThenI will spend a little bit more
(04:36):
time on the terminology and theyare the amyloid beta and tau.
These are the two major factors, so they act as a prion.
This is well studied, wellrecognized, but there is still a
strong debate in the field toconsider it completely fully
prion protein.
(04:56):
So we know, for example, thatif you have neurons, for example
, in culture in the lab, youexpose them to this prion-like
protein, the endogenous protein.
So the endogenous amyloids,endogenous tau.
They start to misfold and thenaggregate.
It's like exactly the prionprotein, exactly the same
(05:19):
principle, but still the fieldis preferred to put a dislike on
the side, because the questionis okay, but if you, for example
, get in contact with those, youwill develop the disease.
This is not what happenedactually, or there are no
evidence on this, like for theprion disease itself, right, but
the principle of spreading orthe formation of the first
(05:43):
aggregates is exactly the sameprinciple.
So you have a beautiful protein.
They do their function for somereason that we still don't know
.
A certain point during ouraging process they misfold, they
acquire the not properstructure and they spread up
this kind of toxic structure toother protein.
(06:04):
Let's say, for example, for tau.
Tau is a very nice protein.
It usually binds a tinystructure within our cells
called microtubules.
These are tubules that keep upwith the cells and maintain
their shape.
So if this tau protein misfolds, basically the cells start to
(06:25):
have some problem and this tau,misfolded tau transmits to the
other tau protein the misfoldedshape.
They start to basically do notfunction properly.
They start to aggregate, theystart to accumulate and later on
these determine the death ofthe cells, in this case of the
(06:46):
neuron, and that's the neuronare not replicative cells.
So when we lost a neuron welost forever.
But think about the crazythings is that this happened in
a very big time lapse for thehumans.
People can with the disease for20 years, 15, 20, 20 years.
So it's a very slow process.
(07:07):
This is why many labs now focuson the early onset of the
disease, when the tau or theamyloid start to form what we
call prionic oligomers.
Speaker 3 (07:23):
So cool.
I have so many questions.
I think every five questionsjust popped into my mind.
Yeah, I'm just kind of somerapid fire for me.
So do you know if animals havealzheimer's disease, or do you
have something comparable in theanimal kingdom?
Speaker 4 (07:37):
so I will answer you with a maybe no means.
I'll'll explain.
I'll explain sopathological-wise.
No animals really develop whathuman develops in terms of
pathology.
There is some study that showup that something that is
(08:00):
comparable to the humanpathology happen in some species
of monkey, and I guess they'recalled marmoset, as I recall.
They're a small monkey, butother animals do not develop
what humans develop.
This could be to the fact thathumans age much longer than
(08:21):
others.
And other animals age naturally,but our aging process is very
how I can say it's been improvedstrongly.
If you think, 100 years ago theaverage of our age wasn't the
one that we have today.
So in a century or in twocenturies we basically doubled
(08:46):
the expense of our life.
So this presented a newchallenge for the neuronal
biology or the brain biologyitself.
This is valid also for otherorgans.
Speaker 3 (08:55):
So my cat just turned 19 and I think she has
Alzheimer's disease.
Sometimes she forgets wherestuff is, so maybe I have this
possibility to challenge thedogma right.
Speaker 2 (09:08):
How many cats live till 19, though she's got a vet
for a dad.
Speaker 1 (09:12):
That's why she's like that's fair, Although I bet if
you put her in an MRI you mightsee other stuff that you.
Speaker 4 (09:18):
Going back to your question, for example, we use
mice as a model.
Mice do not develop naturallyright alzheimer's, so we have to
create a transgenic mice thatbasically reproduce what we
found out.
And this is the reason also why, unfortunately, many clinical
trials do not work out in human.
(09:39):
Because they work perfectlymice, we clean the mice brain
perfectly.
There is a colleague that tomake fun about it, to say we can
cure Alzheimer's in mice.
So this tells you how much iscomplex Study this kind of
disease in animal models likemice, for example.
Speaker 3 (09:58):
Yeah, but the lifespan of a mouse is only two
years, right.
Speaker 4 (10:01):
But they have so many other properties that make
their brain very resilient tothe prion spreading and
aggregation itself, because theypossess, for example, a very
reactive inflammatory responsecompared to the human.
We think right now, in the lastyears, that now inflammation in
(10:22):
the brain play a crucial rolefor the buildup and the early
manifestation of this proteinaggregate.
Speaker 2 (10:29):
So that's what I was going to ask what is driving
that sort of original kind ofmisfolding?
Is it a traumatic brain injury?
Is it inflammation?
Is it like potentially toxicityfrom?
Speaker 4 (10:40):
something.
If I have the answer for thisquestion, I'm not maybe here,
I'm in Sweden receiving theNobel Prize.
So that's a great question, no,look, I report every time an
example I had in my family sideof my grandma and auntie
basically, and she died withAlzheimer's disease.
(11:01):
And this auntie lives in afamily of nine.
There are seven brothers, myauntie and my grandma.
So she developed Alzheimer's onher 60 around.
I love her, it was like asecond grandma for me and she
developed the Alzheimer's.
And my grandma two days ago did99 years old she just made her
(11:23):
birthday and they were sisters.
So the reason lies downprobably to many factors.
These diseases aremultifactorial diseases.
For the last 20 years peoplefocus just on amyloids.
Right, it's the amyloids, theplaques.
We have to block this stuff andwe will cure the disease.
We have to block this stuff andwe will cure the disease.
(11:45):
After 20 years the FDA approvedjust two antibodies for amyloid
and the process is very slow.
But the example of my grandmais just to tell you that they
live in the same family, theyhave the same kind of education,
they have basically also acomparable genetic background.
(12:05):
They were both sisters and onedeveloped Alzheimer's and one
make 99 years.
Speaker 1 (12:11):
And I would assume they both lived a fairly similar
lifestyle as well.
Exactly Similar lifestyle,similar diet similar physical
activity.
Speaker 4 (12:19):
No, physical activity because at the time there were
no gym or they should take carejust of the family.
Very low also education One ofthe risk factors for Alzheimer's
, for example, has beenestablished that low education,
for example.
So if you keep your brain lowwith low activity, so you read
or you do exercise or all thosebrain games that are cool things
(12:40):
that keep up with andcounteract actually the build-up
of this protein.
But the truth is that is amultifactorial thing.
Multifactorial thing and thisbring complexity we we would
like to make in the past easier.
Because you find out prionaggregation.
They usually in the brain formsat the beginning in a very
(13:01):
specific brain region that iscalled the hippocampus and
entorhinal cortex.
This is the region thatgenerally people associate with
the memory.
In fact memory is one of thecognitive dysfunction that
usually people develop inAlzheimer's.
But then what happens is like aprion, once the neurons die, or
through the inflammatory system.
(13:23):
Once the neurons die or throughthe inflammatory system, so
they are called in the brainmicroglia and astrocytic cells,
astrocytes.
So basically it looks likethese cells are not able anymore
to manage the cleanup thatusually occur in our brain
during aging and they alsomediate the spreading across all
the other regions of our brain,the spreading across all the
(13:45):
other regions of our brain, andgradually they bring dysfunction
in many cognitive aspects ofour life.
Speaker 1 (13:51):
So the astrocytes and the microglia assist in the
spreading of these misfoldedproteins.
Speaker 4 (13:56):
Initially they assist to clean up, but at a certain
point, when the system isoverwhelmed, there are theories
that actually make it faster orthere is a strong debate still
on that.
It's very fascinating.
But the job basically is toclean up the microglia.
For example, take care of oursynapses and the synapses are
(14:16):
those portions that connect oneneuron to another neuron and
make us functioning for all ourcognitive or physical activity.
And actually when theseamyloids forms at the beginning
of the disease, the synapsesthat looks like are the most
sensitive parts of our neuronand they burn and microglia
usually come close to thosesynapses that are damaged and
(14:38):
they start to eat.
Clean up all those surroundings,try to keep the neuron as much
as possible functional.
But when you have anoverwhelming amyloid formation
when I say amyloid I includealso the tau protein, the other
component they start to get,let's say they're not able to
manage it anymore and theyacquire some of them.
(15:01):
There is like a beautifulpapers published on it.
Some of these microglia startto became what they call disease
associated microglia, so makethe prion spreading even faster.
Interesting, in fact, in peoplethat have a very fast, I'd say,
first development of thedisease, they have a very strong
microglial activity Interesting, so it's very interesting.
(15:24):
But also the aspects that wehave to consider are so many
that we need to go step by stepon each factor.
Speaker 3 (15:31):
So just to recap, so you were saying with the
microglia, so they normally comein, they clean up, right, and
what I know about prion diseasesis that they accumulate within
the cell and then the cellcannot get rid of them.
So what are you saying is themicroglia come in, they pick up
the disease or the particles ofthe cell that was diseased, and
then they move to a differentplace and they carry the
(15:54):
amyloids with them to adifferent place.
Is that what you're?
Speaker 4 (15:57):
saying yeah, that is one of the mechanisms.
The other mechanism is thatthis transmission happens neuron
by neuron, for example throughthe synapses themselves or
through the secretion ofexosomes or other microvesicles.
Think about that.
This process, as I say, happenslong in time.
Okay, it takes a while.
(16:18):
So our neurons do not dieimmediately, so they have a
certain capacity to rearrange.
Another theory is that, anyway,we form some sort of aggregates
, even in normal aging.
There are cases of people thathave the pathology, for example,
but they do not show anycognitive symptoms or cognitive
(16:39):
impairments.
So there is a system, for sure,that is able to manage even the
presence of the prion andamyloids, the plaques, the
tangles of tau and whatever.
But maybe these people have astronger process that is able to
manage it and the cognitivefunction are still integrated.
(16:59):
But, as to recall, this isalways on the synapses.
But the synapses are verysensitive cellular portion to
the prions because they've beenbinded and then this should work
as a signal for the microglia.
So, okay, this synapses is notproperly working, I'll engulf, I
heat it and then I willdegradate.
But again, which is themicroenvironment around, how the
(17:24):
other, also the astrocytes, areworking up on this.
So this is still underinvestigation and I guess many
new tools and also for thetherapy actually is focusing on
keeping an inflammatory statevery low.
So that is another possibletherapeutic intervention.
Speaker 1 (17:45):
I was going to ask do you know the role that, like
circulation and like good orimproved circulation,
potentially plays in thedevelopment and the progression
of Alzheimer's?
Because I know with otherneurodegenerative diseases
vascularization throughout thebody plays a really big role,
like in maintaining theintegrity of neurons and the
myelin sheaths and stuff likethat.
(18:05):
So is there like a well-knownrole that vascularization plays
in Alzheimer's?
Speaker 4 (18:10):
Yeah, this is a great question.
So there are a study and it'swell-established also that
exists a form of vascularamyloidosis it's called, where
basically the amyloids not onlyform in neurons but form also
and form plaques within theblood vessels.
Now where this comes from theneurons, or is it just the
(18:33):
endothelial cells, for example?
I don't know, but it'srecognized.
It's called CAA cerebralvascular amyloidosis and this is
quite a form that you can findin Alzheimer's as well in
Alzheimer's patients, but notall Alzheimer's patients develop
the deposition of amyloids,because there is also the
possibility that your brain isoverwhelmed with these amyloids.
(18:56):
The spreading is on, andanother way that maybe our body
has to clean up is to flush outthese amyloids through the
vessel.
But again, how much amyloid weare talking about is not just
amyloid, beta, it's tau, Maybeit's even other proteins.
Speaker 3 (19:14):
I like Christina's question, I want to ask
basically from a different angle.
Speaker 2 (19:18):
So we live in a society where so many of us
suffer of bad vascular health,right, atherosclerosis,
hypertension, hypertension andstuff like that and
atherosclerosis for listeners isessentially your blood vessels
are getting clogged, and it isvery common in America and all
over the world.
Speaker 3 (19:37):
Absolutely yes, and thank you for clarifying that.
So is there a correlationbetween bad blood flow to the
brain, or atherosclerosis, andAlzheimer's disease?
It's definitely a risk factor.
Speaker 4 (19:49):
It's definitely a risk factor, but even the
sleeping has been found has animpact on the development of
alzheimer's or form of dementia.
So little sleep is risk factoryeah, I don't know what that
means with bad sleeping, butlike an interrupted sleep or I'm
(20:11):
not an expert on sleeping, butI know that sleeping is playing
a crucial role.
I'm an expert on sleeping.
Another association has beendone with auditory system, and
if you have issues also withyour ear, really yeah, because
that does not stimulate certainparts of your brain and make
(20:31):
your neuron maybe evenvulnerable.
I don't know exactly themechanism, but many aspects of
our lifestyle impact the workingprocess of the brain.
So basically the principleright now, because there is no
cure for this disease, so, likefor other diseases, have a good
lifestyle, eating well.
(20:53):
But this is valid in generalfor any kind of disease, for
cancer, for cardiovasculardiseases and even for dementia.
But again, we discussed beforethe low study or like low
education didn't work out for mygrandma.
She reached 99 years oldwithout any form of dementia.
(21:13):
But again we still need to digmore on the cause.
Maybe we are just seeing theeffects.
Like the amyloid and the prionthemselves is a strong event.
That happened at the beginning.
But we still don't know exactlywhat they are inducing as well.
Human brain is so complex, veryhard to study, so it's very
(21:35):
challenging for me as ascientist in the field exciting
to study.
Speaker 3 (21:42):
So, mauro, I want to come back to your point of the
sleep quality that you refer to,that sleep has an influence on
this.
So there's a new class ofsleeping aids that have been
released now.
Right, we used to have the GABAreceptor-based ones, and
there's now this new class thatbasically reduces your
(22:02):
wakefulness, and I saw there wasan article that speculated on
that.
It actually can help reduceAlzheimer's, and I don't know
what the mechanism is or how itwould avoid accumulation of
amyloid.
Do you think that's a crazyidea?
Have you seen those reportsthat this could?
Speaker 4 (22:20):
be a treatment.
I didn't see those reports, butmaybe it will detect some
impact somehow.
But I don't know.
Honestly, it's hard to say that.
Maybe the other problem is tosee an effect on the incidence
of some therapy or something.
Anyway, you need a larger timewindow.
Maybe this study will, or thetreatment of a particular
(22:42):
compound or something that weregularly use.
The correlation will be foundin 10, 20 years since it's been
developed found in 10, 20 yearssince has been developed.
Speaker 2 (22:56):
So my question with this is I think that there's
always this strong interest incuring in a lot of like
pharmacology stuff, but what youdescribed earlier is that
people can have the pathology ofthis in the brain but not have
symptoms, and so we coexist withthis, or some people can
coexist with this right, Justlike we might have staph on our
skin, but it's not a problem,unless we have a severely deep
cut and then it's in our generalsystem.
Potentially, plaques aren't theproblem if they're not becoming
(23:19):
widespread and your body cankeep up on managing them, right?
So is the interest then inpreventing, like in the field of
Alzheimer's research?
Is the interest in preventingthe plaques from forming at all
or in finding a way to help thebody continue to manage the
plaques that might be formingjust naturally?
Speaker 4 (23:38):
Yeah, that's great.
So the approach at thebeginning, many years ago.
This is why we, the FDA,approved two antibodies right
now available for the amyloidplaques, because many years ago,
with the study of the plaques,scientists say, okay, this is a
difference between an Alzheimercase and a person that do not
(24:01):
have.
So if we maybe we block or wedegraded these plaques, we can
cure the disease.
But again, was not this thecase?
Okay, so imagine also that whenpeople develop plaques or this
is the very final stage.
So to me as a scientist on thefield, it's hard to think about
a cure for late stage.
(24:23):
It's almost impossible becauseat this stage, basically, the
patient already lost.
It's not just the loss ofneurons, but it's the loss of
the connections.
Remember our memories.
Our task has been made by anintricate system that we still
don't know exactly how to workit out.
So when you burn out or youlost that neurons, you could
(24:48):
lose forever those memories.
So thinking about a cure in latestage, I don't think even is
convenient.
So this is why our labs in theMitchell Center, for example, we
are more focused on the earlyphase, where those prions start
to form and they are still smalland toxic, yes, but maybe
(25:09):
targetable in terms of therapy.
And the other is the prevention.
So there are many groups thatare working to identify people
that are vulnerable to thebuildup of these protein
aggregates.
That would be cool.
Maybe we can produce in thenear future a vaccine, a kind of
a vaccine that can prevent, forthose that are more at risk, to
(25:33):
develop dementia.
So that is where the field isgoing using immunotherapy, so
antibody, or, as in our case,starting to use genetic therapy,
so a genetic approachInteresting.
Speaker 2 (25:48):
Could you also clarify the difference between
Alzheimer's and dementia,because I feel like in the
public space, people often usethem in a way that's
interchangeable, but they're notright?
Speaker 4 (25:59):
Yeah, no, they're not .
But with dementia we identifyall those kinds of brain
pathologies that basicallyimpair the brain functionality
at different age.
Okay, because, again,alzheimer's, usually the first
symptoms start around 65 and canlast for longer.
(26:19):
But there are other forms ofdementia, like frontotemporal
dementia, that can develop evenbefore in age.
Okay, so, and that is due to abuildup of other protein.
In this case one of the mostimportant is TDP43, is another
amyloid protein.
So maybe we have to deal evenwith more loidogenic, so
(26:40):
prion-like protein, so that thepicture is more complex.
The Alzheimer's disease in thelast years we are starting to
differentiate also maybe theAlzheimer's disease because
there is an historically,naturally I would like to say
chain, because this isassociated with who discovered
the disease, observed for thefirst time, even within that,
(27:02):
what we call Alzheimer's disease.
We have to differentiate thisform.
But yeah, with form of dementia, we always put Alzheimer's and
many others forms of dementiaand remember these are always
progressive.
So in this umbrella of dementiawe always put Alzheimer's and
many other forms of dementia andremember these are always
progressive.
So in this umbrella of dementia, the disease has to be
progressive.
It's not something that has avery short outcome.
It's long in time, more or less, but it happens in years, and
(27:25):
that has to affect the brain, sothe neurons directly.
Speaker 2 (27:28):
So they're always progressive, but there's no way
to predict how quickly it willprogress for any individual.
Speaker 4 (27:33):
This is also about our genetic background.
This is why we are focusing onthe vulnerability of people.
We are not anymore focused juston those protein aspects.
We have to see our background.
It's like also for many othertype of disease where you could.
Why, for example, people thatmade the same chemotherapy for
(27:54):
the same cancer, someonesurvived, someone not.
There is always a context wherewe have to move and that
context is a personal context, agenetic context.
So there is something thatpotentiates our response and we
can live great with plaques,maybe, like those cases.
And there are contexts whereyour genetics or your
(28:15):
inflammation, your again, thecerebrovascular system is not
working properly for somegenetic reason.
Speaker 3 (28:24):
But, mauro, how far away are we from this
personalized medicine that youtalk about?
Because I think we always hearthat personalized medicine is
the thing of the future.
But I remember, for example, Idid 23andMe this genetic test a
long time ago, right, and I haveone of the, the ApoEG alleles
for early onset Alzheimer'sdisease, but it's just a
(28:46):
slightly increased risk but what?
you were saying is this ismultifaceted, right, it depends
on my sleep and then how I takecare of my body, and so on.
So it feels like we're stilllike in the childhood, in the
baby days of personalizedmedicine.
When it comes to dementia, theresearch is all right.
Speaker 4 (29:04):
Yeah, I agree with you, Big progress has been done
in terms of a variety ofpossible therapeutic
intervention.
In terms of variety of possibletherapeutic intervention.
In Dr Kaya's lab, actually, wedevelop an immunotherapy for tau
, not for amyloid that worksperfectly nice.
So hopefully we will test itout in humans as well, with some
(29:24):
clinical trials.
But again, this is a generaltherapy, so it's something that
you apply for everyone.
As you say, I've been heardabout like personal therapy,
even in cancer now 10 years ago,but even there has been like
very challenging as well.
So I guess that for this typeof disease, find a common
(29:46):
mechanism or mechanism-basedtherapy will be a winning card,
or mechanism-based therapy willbe a winning card.
But in terms of years, I thinkthat maybe we will see some
significant impact on the newtherapies within five, ten years
.
Maybe that's the window that Iexpect, looking about the
progress that others are doingwith several types of therapies.
(30:09):
But it's very challenging andagain, and this is why I'm
focused more on the biology westill move our vision a little
bit, I don't want to say faraway from the prion or from the
protein aggregates, but also onthe genetic aspect and how the
genes answer to these proteinaggregates.
(30:30):
Because, maybe the proteinaggregates is not just the cause
, it's just the input to acascade of things that then
determine the death of theneurons in our brain.
Speaker 2 (30:40):
Speaking of inputs that can cause cascades, I
wanted to get your opinion on ifyou think we'll see an increase
in Alzheimer's in ourpopulation because we've had
COVID, which is a neuroinvasivevirus, so it can infect the
brain and COVID can act like atraumatic brain injury right,
and it could certainly causeinflammation.
Do you think we'll see anincrease in Alzheimer's like 20,
(31:03):
40, 60 years down the line?
Speaker 4 (31:04):
I don't know if we will see that increase.
We need to wait a little bit.
Covid happened a few years ago.
Okay, as I say, this diseaseparticular, alzheimer's requires
several years, but there arebeautiful studies that talk
about how a previous infectionfrom other viruses or even
bacteria in the brain can bringvulnerability for the developing
(31:28):
of dementia.
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