September 11, 2025 • 27 mins
Neurodegenerative disease doesn’t begin in your seventies—it builds over a lifetime. In this episode, physician-scientist Dr. Fanny Elahi explores why women face a higher risk of Alzheimer’s, the connection between hormones, stress, and brain aging, and how her lab at Mount Sinai is advancing early detection with blood biomarkers. She also explains why menopause is a crucial time for women’s brain health and the daily habits that can help protect memory and cognitive function.
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Speaker 1 (00:01):
Welcome to hear something good on women's health and longevity.
We are so grateful to our partners P ANDNG, maker
of trusted brands like Tampex Always and Always Discreet, and Walgreens,
the women's well being destination, supporting every stage. Together, we'll
bring you something good each week on women's health and longevity,
and it wouldn't be possible without their support. Each week,
(00:23):
we aspire to bringing the good news on women's health
by talking to renowned scientists and medical experts, and by
sharing health advice that can help you live healthier and happier. Today,
we're talking about something that some consider a women's disease, Alzheimer's.
Two thirds of all people with the condition are women.
The risk for women to develop dementia over their lifetime
(00:45):
is a stunning one in five. Worrisome, yes, but if
you're looking for hope, our guest today brings good news.
Doctor Fannie Alahi is a renowned leader in the fight
against Alzheimer's and dementia. She's a physician, scientist, and Sociate
Professor of Neurology in Neuroscience at Mount Sinai in New York. There,
she leads the Alahi Lab where she and her team
(01:06):
of scientists worked to develop new therapies to protect brain function.
My conversation with doctor Olahi took place during a recent
women's health and longevity salon hosted by Seneca in New
York City.
Speaker 2 (01:19):
Welcome, doctor o'lachey, Thank you so much.
Speaker 1 (01:21):
So of course we all know the statistics Alzheimer's neurodegender
disease can be a women's disease, and you've started to
focus your research on the role of female sex hormones.
What is the connection and why are you doing this.
Speaker 3 (01:34):
I didn't start my career studying sex differences or women's
risk of all Zheimer's disease, first of all, because I
was not taught the statistics.
Speaker 2 (01:44):
So I just followed my curiosity.
Speaker 3 (01:47):
One thing led to another, and I ended up becoming
a specialist in neuroggenitive diseases, partly because of the burden
and the unanswered questions and the wave of new tech
technology and tools at our disposal to go back and
ask those old questions and have stand a chance of
actually getting somewhere. So that's how I ended up setting
(02:10):
ner dejective diseases, and I thought Alzheimer's disease was figured out.
It's one of the diseases that, yeah, they got that,
and so most of the time when they got that,
I don't do it right. It doesn't make sense to
put your energy and sort of build a career. And
then little by little, you know, I realized that it's
kind of scary because Alzheimer's disease has been reduced to
(02:33):
two proteins for which we now have treatments. One actually
has two drugs with FDA approval. This is a drug
that is lowering amyloid from the brain and the other
being TAO, thought to be the more toxic protein, has
drugs in development and in clinical trials. Then, while it's
good to have something for Alzheimer's disease, we now know
(02:55):
from the clinical trials and from the treatments that they
are not.
Speaker 2 (02:59):
Going to stop the disease.
Speaker 3 (03:01):
We don't understand why someone develops Alzheimer's disease, and genetics
is only part of it, and a really really really
tiny part when you actually think about late life onset disorders,
even a smaller part is genetics, and a lot more
is environmental. In the bucket of environmental, I want to
(03:23):
put stress, which now has exciting, robust biology that is
coming to the surface. And given all the statistics and
all the facts that you state to it, I cannot
help a thing that part of women's risk of developing
this late life disorder is surviving and here thriving despite
(03:46):
the stress. But we feel it, and that stress is
impacting our biology. We survive it and we live longer.
Sometimes sadly, if we have disease, we live longer. We
outlive men, but with burden of life life nerd degenctive
disease that eventually leads to dementia. What I have also
been very fascinated with is a part of the brain
(04:07):
that is called white matter. It's the insulation of the
nerve cells. So most of neurodegenctive disease has been focused
on the neurons, the cells, the main cells of the
brain dying. But the question is why do they die.
We have them when we're born. We actually have more neurons.
We lose them as we live, as we start creating.
Speaker 2 (04:29):
Our habits, learn become our person.
Speaker 3 (04:34):
We have these neuronal networks that are quite fixed, and
things get modified. We can still add and deduct, but
for the most part, we have our brain cells there
they start dying. The question is why do they start
dying at a random time in our lifespan. So as
really really fascinated with that question, and it's not necessarily
(04:56):
a logical chain of ideas, but it became quite clear
to me that one of the most neglected parts of
the brain are the blood vessels. They're not considered part
of the brain actually, right, So when you talk about
the model systems that we have, the stem cell models
that we've developed and all the tools that we have,
you can study neurons really well. You can study now
(05:18):
the support cells called glia. We now have at liuses.
These are like encyclopedic level of information about the identity
of the brain cells and what is triggering them and
killing them all for these kinds of cells. Now most
of your brain is actually all of every cell is perfused.
(05:39):
Blood comes from your body in a very intricate system
and is delivered to these cells. Those are the blood vessels.
They are very very dynamic and they're in constant exchange
with the environment. So if anything feels that exposomics your environment.
(05:59):
Are cells they're supposed to guard to the brain, but
we know that with age they change, and so I
became incredibly fascinated with that, and I realized that we
know nothing, I mean, compared to what we know about
the rest of the brain. We actually know really nothing
about them. One interesting fact about Alzheimer's disease is that
it has a really robust vascular component, but really hypertension
(06:21):
is one of the major ris factors. Just Alzheimer's disease
itself has this component called steerable amyloid angiopathy. It's the
blood vessel disease component of Alzheimer's disease, and we don't
have a way to detect it until it gets really bad,
so we've never been able to track it. We've never
been able to enter it into our models. These models
(06:44):
tell us where the problem is, so if you don't
enter that element in your model, you will never discover
that it's a driving force behind the decline of the
brain function. So our models have really just led to
the development of these two drugs, and we have not
allowed any other answers to come to the surface.
Speaker 2 (07:04):
So part of my lab started developing these tools.
Speaker 3 (07:06):
And as we started developing these tools, we made discoveries
with regards to some biology that led me to study
preeclamsia because.
Speaker 2 (07:17):
These same.
Speaker 3 (07:20):
Molecular problems have been observed and are now part of
an FDA approved biomarker strategy for diagnosing preeclamsia.
Speaker 1 (07:30):
Woman, So I'm going to stop you for a minute.
Speaker 2 (07:33):
There's a lot more y good thing to stop me.
Speaker 1 (07:35):
Well, I'm going to stop you for a minute just
for definitions. So you are an expert in biomarkers, and
what really struck me, what you sort of enlightened me
about I would say maybe seven or eight years ago.
I feel I have an advantage is that neurodogeneral disease
doesn't get laid down in your seventies. You don't just
get neurodogenital disease in your seventies, which is.
Speaker 2 (07:56):
What I thought, right. I thought, like, okay, well.
Speaker 1 (07:58):
We'll see how it goes, and then when I'm in
my seventies, will see if I have Alzheimer's. In fact,
to your point, what you do earlier in life actually
can make a difference. And so the other thing that
I learned from you was the importance of biomarker testing
and the fact that you are in the biomarker discovery practice.
Shall I say and the fact that there will be
ways potentially to understand your trajectory sooner. Can you talk
(08:21):
to us about blood biomarkers and why this sort of
time horizon is so important.
Speaker 3 (08:26):
Yeah, so I know that the world is excited about AI.
Speaker 2 (08:29):
I'm excited about biomarkers.
Speaker 3 (08:31):
I think I think they're the true game changing tool
that we have at our disposal.
Speaker 2 (08:36):
And so what are biomarkers.
Speaker 3 (08:37):
They're basically markers that are marking biology. So these can
be anything from structural changes in your brain that you
can get through a magnetic resonance imaging an MRI and
imaging of your brain that we've been able to do
for a long time, but that's a static picture of
(08:58):
the brain, molecular measures and so for cancer, you know,
they've been around for some time. And in fact, a
lot of these tools, terminologies, and concepts come from fields
like cancer to nerdegenative diseases where we actually have drugs
and we've discovered things to target. The neurodegenative diseases like
cancer and other disorders are incredibly complex, but with the
(09:22):
additional barrier of not being in an accessible organ so
you cannot go and buyop see someone's brain, although when
things get really bad sometimes that is done. Most of
the time, we can't buy and see the brain, So
how can we know what's going on in the brain
If memory is not just Alzheimer's diseases, everything can can
impact these functions. So first we need a serble spinal fluid,
(09:48):
and in that spinal fluid we would measure specific molecules
that would give us the diagnosis of Alzheimer's disease without
saying why a brain developed Alzheimer's disease. Then ligands were
developed and we could do this through imaging called pet scan,
So pet amyloid was developed. It's a radioactive dye. You
(10:09):
get it injected and you can see it on imaging. Great,
it's not invasive, you no longer need a lumbar puncture,
incredibly expensive and so prohibitive to actually do it at
scale at population level. And then finally we were able
to measure these molecules in blood so ad mound SEINAI.
We now are one of eight internationally that have brought
(10:32):
the blood BUYO markers into clinic and they've been absolutely
game changing because you can think that you would think
maybe five times you would try to dissuade yourself that
you have a symptom. If lumber puncture is your way,
you know, a needle in your spine to get fluid
out is your way to get the diagnosis. And PET
scan is similarly cost prohibitive, but now that you can
(10:54):
do it in blood for two hundred three hundred bucks,
but when it hits clinic it's going to be really cheap.
Speaker 2 (11:02):
More people are going to seek diagnosis.
Speaker 3 (11:04):
And what that means is that we're going to be
able to detect this well before things are irreversible, is
my hope. And so this is the start. What we're
doing in the lab is we want to expand this.
You know, these two proteins, this tip of the iceberg
Alzheimer's diagnosis is and end stage problem.
Speaker 2 (11:26):
If you expand it to hundreds.
Speaker 3 (11:28):
Of molecules that we have biology for for which we
can develop treatments, it's going to be truly game changing.
So what I envisioned for the future is that you
think you're at an age you know at which you
would be at risk no symptoms, you get this screening
tool similar to mimmography. You can screen for pathology before
(11:50):
your function has declined or when you start thinking, am
I not remembering the name right just because this is aging?
Or is this really the beginning of something? You get
the screening.
Speaker 1 (12:03):
So to me, that kind of changed my whole thinking
about aging and longevity. I mean, the idea that you
could intervene early, you could detect early through different life stages,
which kind of brings me to the topic that we're
all very excited about, which is the intersection between sex
hormones and aging and hopefully not pathology, but what is
(12:25):
the intersection between menopause perimenopause. What are you starting to
see and what are you studying?
Speaker 3 (12:31):
So how we got there is through these the discovery
of these molecules that are abnormally regulated in the aging brain,
these were age brains.
Speaker 2 (12:43):
And then we looked at the data.
Speaker 3 (12:46):
Well, how we got there was very interesting. So we
kept on looking at the data and we saw no association.
Speaker 2 (12:51):
Nothing.
Speaker 3 (12:51):
Now it was a mud until we said, look, we
have women, men, young and old in this data sets
unique because most of the time, if not always, for
brain outcomes related to Alzheimer's and dementia, it's individuals sixty
five and above. So you don't have menopause, you don't
(13:12):
have younger women, you don't capture that transition. But anyway,
so we had for the first time, by certaindipity, a
group of individuals that spanned lifespan to a certain extent,
that were in their forties and older. And once we
build these specific statistical models where we looked at is
going to be get technical, but interaction of sex and age,
(13:36):
we saw biology robust associations of these molecules with brain outcomes.
The molecules are regulating the flexibility and the health of
blood vessels. And what we showed is that as the
blood vessel flexibility we call it plasticity changes, the directionality
(13:58):
of the association of these molecules change. In younger women,
higher levels were associated with better function, better brain outcome, structural, functional,
all of it, and as we age it.
Speaker 2 (14:07):
Was the opposite.
Speaker 3 (14:10):
This is all correlative, so we still don't understand and
this was robust in women. For men, it didn't actually
really matter whether they were young or old. The associations
were always almost in the same direction and not that robust,
not that impressive. There's also a gene. It has multiple
different forms, and the risk form is called apo E four.
(14:31):
That's the risk allele, and it really is especially a
risk factor for women's risk of developing Alzheimer's disease. And
when we looked at women who carried this risk alile,
then the associations were even more robust. So when I
started looking at started educating myself with regards to these
(14:55):
molecules and what they do, every single paper that I found,
every single one without exception, was on pre clamsia, this
condition that is deadly for women. They spontaneously develop hypertension,
high blood pressure, headache, strokes, and they could die if
intervention is not childmove from childbirth during pregnancy, it's later
(15:15):
stages of pregnancy. And so I thought, isn't this fascinating?
There is something about this biology that is specifically female.
So even if I didn't care about women's risk o baby,
which I did, the data really brought us into that realm.
And we started talking to obgyn specialists to understand hormones.
(15:38):
What's actually happening during pregnancy? Do we even understand And
the answer was, we don't even understand why women develop
pre clumsia. We still can't predict that. We don't understand it,
but we know some things about what we could go after.
Speaker 1 (15:53):
I think what's amazing is that we kind of assume
that people have got this, you know that like people
thought about this in the past. It's been studying women's
brain health. Shouldn't be such a novel concept, but yet
here we are today, and I think it's amazing. We
talk about the lack of data sets, and we always
kind of joke that even male mice didn't have a
seat at the table because we weren't even using you know,
(16:13):
female mice and experiments until relatively recently. In fact, Fanny
was the first person to use female stem cells in
the research. So that's why I'm blowing and them yes please,
And that's been just an amazing discovery.
Speaker 3 (16:26):
NIH and other mainly ANIH funded this incredibly visionary initiative
to create stem cells to study neurodegenative diseases. You know,
you can't sample someone's brain, so you can take stem
cells from them and create a brain in a dish.
You can create blood vessels in a dish. You can
recreate a lot of different things, and as we go forward,
(16:49):
we can do more and more and this is really
a game changing tool. So I was very excited to
start using stem cells in this resource three hundred plus
lines is in with all sorts of mutations everything. It's
one Northern European man in their fifties who donated their
(17:09):
selves and there is no equivalent.
Speaker 2 (17:12):
There is no female line. That's it.
Speaker 3 (17:15):
Imagine all the discoveries. This is taking us back to
when we started using mice. Every single scientific discovery is
going to be one hundred percent valid for that individual
to a certain extent, generalizable and you can extrapolate it
to the rest of people who would share that genotype
and background, but really not helpful if you're stuttying sex
(17:36):
differences or women's specific risk of all zeimercy these But
what's maybe more mind blowing than that. And so thanks
to the funding that we were able to receive, we
created initially by serendipity, every line that I created was female.
Speaker 2 (17:52):
It was not planned.
Speaker 3 (17:54):
It was just like every donor that I had in
the research that I created line. And then I was like, well,
we're going to create a resource that we're going to
make available to the scientific community that's going to be female.
But what was absolutely mind blowing is that this is
for the studies of neudugantive diseases with Alzheimer's being the
most common, and no one thought, shouldn't this be a
(18:16):
female line. If we're going to take one line, shouldn't
it be a female line. If we're going to go
after Alzheimer's disease as our goal. That's just mind blowing.
Speaker 1 (18:24):
We're at this critical moment where we have women's scientists
at this level who are discovering things in a moment
where it literally could change you know, the people in
this room. Our lives could be very different because of
the work that Doctorali is doing. And I really have
to thank you for the tireless work because I know,
with two young daughters and unbelievable long nights in the
(18:46):
lab and an obsession to solve this for all of us,
it's really remarkable to know you and to know your work.
Tell us about the IRB approvals that you recently got, well, I.
Speaker 3 (18:56):
Think the timing is really fascinating, right, because we've been
struggling with the ir BE.
Speaker 2 (19:00):
This is a regulatory.
Speaker 3 (19:01):
Approval to bring in human subjects and collect the data.
Speaker 2 (19:05):
I'm not kidding you.
Speaker 3 (19:07):
It's been just one thing after another, reversing and going back.
So I was almost ready to say, let's put a
pause on this, let's move on with the other projects
and come back.
Speaker 2 (19:17):
But we got approval last week. This is the mind menopause, menopause,
Mind matter.
Speaker 1 (19:26):
Menopause mind matter study. Yeah, and what's so exciting about
this is this is one of the first studies that's
going to really triangulate between brain health and women's sex differences.
And so again she's been waiting for months for approval,
got the funding, just recently got the initial funding at least,
just got the approval for this study, and is limited
(19:47):
to one hundred people to be part of this through perimenopause, menopause,
and postmenopause.
Speaker 3 (19:54):
Right, So every question that we start asking, we try
to access worldwide data whatever is available to us. That's
the fast this way. Then we use that data to
design experiments. But in this case, there was no data
to be accessed because again most of these large data
sets that have good phenotyping of the brain is sixty
five and above.
Speaker 2 (20:13):
So we don't actually.
Speaker 3 (20:14):
Know what that period in women's life where there's this
massive transition and hormonal states do, what the relationship between
that and the brain outcomes, namely Alzheimer's disease is, and
what role do hormones play And the reason why we
(20:34):
were really interested in hormones is that you can actually
intervene on that.
Speaker 2 (20:37):
So if we can understand which hormones in what combination,
in what dosage, and now that we have these blood
readouts of disease, we can really start asking these questions
in human beings as opposed to mice, rats and models,
and then understand how to intervene go back to those
(20:59):
models and see what you can actually change some of
the pathology. So that's why we needed to create this cord.
Speaker 3 (21:04):
And we hope that one hundred is not enough, but
this is what we can start with, and we really
hope that we can create this resource not just for
our own questions, but for the world to come and
ask very specific questions with regards to women's brain aging trajectory.
Speaker 1 (21:20):
The last thing I wanted to just ask you while
I have you, since we're talking about women's health and longevity,
what can you do? What can you do at any
age to expand your lifespan to health span? What are
the practices, the daily practices that can help each of
us right now as we're thinking about our brain health.
Speaker 3 (21:35):
I always used to start by saying exercise. It's true,
and we'll come back to that. But I want to
see reduce stress, and by that I mean reduce bad stress.
Not the stress that gets you activated and successful in life,
the stress where you feel trapped and helpless. I think
that kind of stress, aggressively lowering it through building the
(21:59):
community and support. But I want to come back to
exercise because that's a way to build it actually and
to counter this bad stress. So why exercise is the
single most important health measure across diseases, especially brain But
I think across diseases is not understood, and there are
(22:21):
a lot of great friends of mine who are trying
to discover the molecules and bottle it because that would
be the blockbuster. I mean, that just would be the
Nobel laureate unanimously. We don't want to exercise all the time.
I exercise, but every single time I would rather do
something else every single time. And I always envy those
(22:44):
who enjoy exercise so much that they need to get
pulled out of the gym.
Speaker 2 (22:48):
That's not me.
Speaker 3 (22:50):
So I don't know what it does, but it's more
than just molecules. I mean some of the things we
know bones are incredibly important for the brain. And so
when you're actually exercising, so strength training, not just cardiovascular exercise,
but strength training, when your muscles are sort of pulling
on the bone, there's a lot of action in the
bones that impacts the brain almost quite directly. You know,
(23:14):
biology is not as fixed as we used to think
about it, and so there's this like rebooting. It's almost
doing a little bit of violence to yourself, right, And
we know through epidemiological studies that when infections were around
and we were less sterile, we also did better with
regards to cardiovascular disease.
Speaker 2 (23:33):
And so this sort of sterile.
Speaker 3 (23:35):
Stressful environment is not good for our organs, including the brain.
So if you took someone's blood right after exercise, inflammation
markers are really high. But in the long run your
inflammation comes down. But the long run, you reset your
physiology and is a much healthier physiology. So exercise, exercise, exercise, exercise,
(24:00):
but strength training and then sleep and that's harder. But
if you do have control over some factors for your sleep,
control them sleep hyrogen, you know, not stressful things right
before going to bed where they can wake you up
in the middle of the night or keep you going,
so sleep hyrogen and being able to control what you
(24:20):
can control is important. Sleep apnea getting tested for that.
You could be incredibly thin and fit and have sleep apnia.
So if you're waking up in the middle of the
night or you don't feel refreshed, get tested for your sleep.
Diet is more complicated, but I think the principles of
avoiding simple sugars and carbohydrate and the Mediterranean like diet
(24:44):
is probably works. Vegetarian diet if you can do it
really well, which is hard, and you're not lacking in
nutrients and vitamins, could be helpful. So I think diet,
the jury is still out and I don't give any
dietary advice beyond avoid sugar.
Speaker 2 (25:02):
Alcohol. I don't think anyone thinks is good for your brain.
Speaker 3 (25:05):
But for my patients whose lifestyle is really linked to
that one glass of wine, I don't take it away
from them because I don't think we have enough data
on that. But I think each individual knows what's good
for them. Smoking is clearly not good for everyone or anyone, right,
and there's a lot of controversy with regards to fat
(25:26):
in general, so I don't think we understand it very well.
I think cholesterol and lipids have a very complicated biology
and not all of.
Speaker 2 (25:35):
It is what you actually eat.
Speaker 3 (25:38):
And I don't think anyone is like deep frying food
every day and eating them.
Speaker 1 (25:42):
But if you are, probably don't want to do that.
But you don't want to do the idea of my
brain being in her hands makes me feel very good.
It makes me sleep really well at night.
Speaker 2 (25:53):
Thanks so much for doing it. Thank you, Katty.
Speaker 1 (25:58):
What an amazing and full conversation. Doctor Olahi is doing
work that can improve life for everyone. Here are my
top takeaways. First, Alzheimer's is a woman's health issue. Two
thirds of those affected are women, and it seems that
women's scientists like doctor Olahi will find a way to
conquer it by looking at women's specific biology and hormones
(26:20):
and by studying the connection between conditions like menopause and Alzheimer's. Second,
we're already seeing game changers in the detection of Alzheimer's. Previously,
an expensive and uncomfortable spinal tap was necessary for early detection. Now,
says doctor Olahi, blood based biomarker testing can find the
(26:40):
disease sooner, more cheaply, and less invasively. Hopefully leading to
diagnosis before things become irreversible. Lastly, while genetics plays some
part in the development of Alzheimer's, environment is a huge
factor That means we can lessen our risk for the
disease by managing stress, getting plenty of e X, your
size and sleep, and maintaining a healthy diet. Have a
(27:03):
great day. For more podcasts from iHeartRadio, check out the
iHeartRadio app, Apple Podcasts, or wherever you listen to your
favorite shows. Today's episode of Here's Something Good on women's
health and longevity was brought to you by p ANDNG,
maker of trusted brands like Tampax Always and Always Discreet,
and by Walgreens, the women's well being destination, supporting every
(27:26):
stage
Welcome to hear something good on women's health and longevity.
We are so grateful to our partners P ANDNG, maker
of trusted brands like Tampex Always and Always Discreet, and Walgreens,
the women's well being destination, supporting every stage. Together, we'll
bring you something good each week on women's health and longevity,
and it wouldn't be possible without their support. Each week,
(00:23):
we aspire to bringing the good news on women's health
by talking to renowned scientists and medical experts, and by
sharing health advice that can help you live healthier and happier. Today,
we're talking about something that some consider a women's disease, Alzheimer's.
Two thirds of all people with the condition are women.
The risk for women to develop dementia over their lifetime
(00:45):
is a stunning one in five. Worrisome, yes, but if
you're looking for hope, our guest today brings good news.
Doctor Fannie Alahi is a renowned leader in the fight
against Alzheimer's and dementia. She's a physician, scientist, and Sociate
Professor of Neurology in Neuroscience at Mount Sinai in New York. There,
she leads the Alahi Lab where she and her team
(01:06):
of scientists worked to develop new therapies to protect brain function.
My conversation with doctor Olahi took place during a recent
women's health and longevity salon hosted by Seneca in New
York City.
Speaker 2 (01:19):
Welcome, doctor o'lachey, Thank you so much.
Speaker 1 (01:21):
So of course we all know the statistics Alzheimer's neurodegender
disease can be a women's disease, and you've started to
focus your research on the role of female sex hormones.
What is the connection and why are you doing this.
Speaker 3 (01:34):
I didn't start my career studying sex differences or women's
risk of all Zheimer's disease, first of all, because I
was not taught the statistics.
Speaker 2 (01:44):
So I just followed my curiosity.
Speaker 3 (01:47):
One thing led to another, and I ended up becoming
a specialist in neuroggenitive diseases, partly because of the burden
and the unanswered questions and the wave of new tech
technology and tools at our disposal to go back and
ask those old questions and have stand a chance of
actually getting somewhere. So that's how I ended up setting
(02:10):
ner dejective diseases, and I thought Alzheimer's disease was figured out.
It's one of the diseases that, yeah, they got that,
and so most of the time when they got that,
I don't do it right. It doesn't make sense to
put your energy and sort of build a career. And
then little by little, you know, I realized that it's
kind of scary because Alzheimer's disease has been reduced to
(02:33):
two proteins for which we now have treatments. One actually
has two drugs with FDA approval. This is a drug
that is lowering amyloid from the brain and the other
being TAO, thought to be the more toxic protein, has
drugs in development and in clinical trials. Then, while it's
good to have something for Alzheimer's disease, we now know
(02:55):
from the clinical trials and from the treatments that they
are not.
Speaker 2 (02:59):
Going to stop the disease.
Speaker 3 (03:01):
We don't understand why someone develops Alzheimer's disease, and genetics
is only part of it, and a really really really
tiny part when you actually think about late life onset disorders,
even a smaller part is genetics, and a lot more
is environmental. In the bucket of environmental, I want to
(03:23):
put stress, which now has exciting, robust biology that is
coming to the surface. And given all the statistics and
all the facts that you state to it, I cannot
help a thing that part of women's risk of developing
this late life disorder is surviving and here thriving despite
(03:46):
the stress. But we feel it, and that stress is
impacting our biology. We survive it and we live longer.
Sometimes sadly, if we have disease, we live longer. We
outlive men, but with burden of life life nerd degenctive
disease that eventually leads to dementia. What I have also
been very fascinated with is a part of the brain
(04:07):
that is called white matter. It's the insulation of the
nerve cells. So most of neurodegenctive disease has been focused
on the neurons, the cells, the main cells of the
brain dying. But the question is why do they die.
We have them when we're born. We actually have more neurons.
We lose them as we live, as we start creating.
Speaker 2 (04:29):
Our habits, learn become our person.
Speaker 3 (04:34):
We have these neuronal networks that are quite fixed, and
things get modified. We can still add and deduct, but
for the most part, we have our brain cells there
they start dying. The question is why do they start
dying at a random time in our lifespan. So as
really really fascinated with that question, and it's not necessarily
(04:56):
a logical chain of ideas, but it became quite clear
to me that one of the most neglected parts of
the brain are the blood vessels. They're not considered part
of the brain actually, right, So when you talk about
the model systems that we have, the stem cell models
that we've developed and all the tools that we have,
you can study neurons really well. You can study now
(05:18):
the support cells called glia. We now have at liuses.
These are like encyclopedic level of information about the identity
of the brain cells and what is triggering them and
killing them all for these kinds of cells. Now most
of your brain is actually all of every cell is perfused.
(05:39):
Blood comes from your body in a very intricate system
and is delivered to these cells. Those are the blood vessels.
They are very very dynamic and they're in constant exchange
with the environment. So if anything feels that exposomics your environment.
(05:59):
Are cells they're supposed to guard to the brain, but
we know that with age they change, and so I
became incredibly fascinated with that, and I realized that we
know nothing, I mean, compared to what we know about
the rest of the brain. We actually know really nothing
about them. One interesting fact about Alzheimer's disease is that
it has a really robust vascular component, but really hypertension
(06:21):
is one of the major ris factors. Just Alzheimer's disease
itself has this component called steerable amyloid angiopathy. It's the
blood vessel disease component of Alzheimer's disease, and we don't
have a way to detect it until it gets really bad,
so we've never been able to track it. We've never
been able to enter it into our models. These models
(06:44):
tell us where the problem is, so if you don't
enter that element in your model, you will never discover
that it's a driving force behind the decline of the
brain function. So our models have really just led to
the development of these two drugs, and we have not
allowed any other answers to come to the surface.
Speaker 2 (07:04):
So part of my lab started developing these tools.
Speaker 3 (07:06):
And as we started developing these tools, we made discoveries
with regards to some biology that led me to study
preeclamsia because.
Speaker 2 (07:17):
These same.
Speaker 3 (07:20):
Molecular problems have been observed and are now part of
an FDA approved biomarker strategy for diagnosing preeclamsia.
Speaker 1 (07:30):
Woman, So I'm going to stop you for a minute.
Speaker 2 (07:33):
There's a lot more y good thing to stop me.
Speaker 1 (07:35):
Well, I'm going to stop you for a minute just
for definitions. So you are an expert in biomarkers, and
what really struck me, what you sort of enlightened me
about I would say maybe seven or eight years ago.
I feel I have an advantage is that neurodogeneral disease
doesn't get laid down in your seventies. You don't just
get neurodogenital disease in your seventies, which is.
Speaker 2 (07:56):
What I thought, right. I thought, like, okay, well.
Speaker 1 (07:58):
We'll see how it goes, and then when I'm in
my seventies, will see if I have Alzheimer's. In fact,
to your point, what you do earlier in life actually
can make a difference. And so the other thing that
I learned from you was the importance of biomarker testing
and the fact that you are in the biomarker discovery practice.
Shall I say and the fact that there will be
ways potentially to understand your trajectory sooner. Can you talk
(08:21):
to us about blood biomarkers and why this sort of
time horizon is so important.
Speaker 3 (08:26):
Yeah, so I know that the world is excited about AI.
Speaker 2 (08:29):
I'm excited about biomarkers.
Speaker 3 (08:31):
I think I think they're the true game changing tool
that we have at our disposal.
Speaker 2 (08:36):
And so what are biomarkers.
Speaker 3 (08:37):
They're basically markers that are marking biology. So these can
be anything from structural changes in your brain that you
can get through a magnetic resonance imaging an MRI and
imaging of your brain that we've been able to do
for a long time, but that's a static picture of
(08:58):
the brain, molecular measures and so for cancer, you know,
they've been around for some time. And in fact, a
lot of these tools, terminologies, and concepts come from fields
like cancer to nerdegenative diseases where we actually have drugs
and we've discovered things to target. The neurodegenative diseases like
cancer and other disorders are incredibly complex, but with the
(09:22):
additional barrier of not being in an accessible organ so
you cannot go and buyop see someone's brain, although when
things get really bad sometimes that is done. Most of
the time, we can't buy and see the brain, So
how can we know what's going on in the brain
If memory is not just Alzheimer's diseases, everything can can
impact these functions. So first we need a serble spinal fluid,
(09:48):
and in that spinal fluid we would measure specific molecules
that would give us the diagnosis of Alzheimer's disease without
saying why a brain developed Alzheimer's disease. Then ligands were
developed and we could do this through imaging called pet scan,
So pet amyloid was developed. It's a radioactive dye. You
(10:09):
get it injected and you can see it on imaging. Great,
it's not invasive, you no longer need a lumbar puncture,
incredibly expensive and so prohibitive to actually do it at
scale at population level. And then finally we were able
to measure these molecules in blood so ad mound SEINAI.
We now are one of eight internationally that have brought
(10:32):
the blood BUYO markers into clinic and they've been absolutely
game changing because you can think that you would think
maybe five times you would try to dissuade yourself that
you have a symptom. If lumber puncture is your way,
you know, a needle in your spine to get fluid
out is your way to get the diagnosis. And PET
scan is similarly cost prohibitive, but now that you can
(10:54):
do it in blood for two hundred three hundred bucks,
but when it hits clinic it's going to be really cheap.
Speaker 2 (11:02):
More people are going to seek diagnosis.
Speaker 3 (11:04):
And what that means is that we're going to be
able to detect this well before things are irreversible, is
my hope. And so this is the start. What we're
doing in the lab is we want to expand this.
You know, these two proteins, this tip of the iceberg
Alzheimer's diagnosis is and end stage problem.
Speaker 2 (11:26):
If you expand it to hundreds.
Speaker 3 (11:28):
Of molecules that we have biology for for which we
can develop treatments, it's going to be truly game changing.
So what I envisioned for the future is that you
think you're at an age you know at which you
would be at risk no symptoms, you get this screening
tool similar to mimmography. You can screen for pathology before
(11:50):
your function has declined or when you start thinking, am
I not remembering the name right just because this is aging?
Or is this really the beginning of something? You get
the screening.
Speaker 1 (12:03):
So to me, that kind of changed my whole thinking
about aging and longevity. I mean, the idea that you
could intervene early, you could detect early through different life stages,
which kind of brings me to the topic that we're
all very excited about, which is the intersection between sex
hormones and aging and hopefully not pathology, but what is
(12:25):
the intersection between menopause perimenopause. What are you starting to
see and what are you studying?
Speaker 3 (12:31):
So how we got there is through these the discovery
of these molecules that are abnormally regulated in the aging brain,
these were age brains.
Speaker 2 (12:43):
And then we looked at the data.
Speaker 3 (12:46):
Well, how we got there was very interesting. So we
kept on looking at the data and we saw no association.
Speaker 2 (12:51):
Nothing.
Speaker 3 (12:51):
Now it was a mud until we said, look, we
have women, men, young and old in this data sets
unique because most of the time, if not always, for
brain outcomes related to Alzheimer's and dementia, it's individuals sixty
five and above. So you don't have menopause, you don't
(13:12):
have younger women, you don't capture that transition. But anyway,
so we had for the first time, by certaindipity, a
group of individuals that spanned lifespan to a certain extent,
that were in their forties and older. And once we
build these specific statistical models where we looked at is
going to be get technical, but interaction of sex and age,
(13:36):
we saw biology robust associations of these molecules with brain outcomes.
The molecules are regulating the flexibility and the health of
blood vessels. And what we showed is that as the
blood vessel flexibility we call it plasticity changes, the directionality
(13:58):
of the association of these molecules change. In younger women,
higher levels were associated with better function, better brain outcome, structural, functional,
all of it, and as we age it.
Speaker 2 (14:07):
Was the opposite.
Speaker 3 (14:10):
This is all correlative, so we still don't understand and
this was robust in women. For men, it didn't actually
really matter whether they were young or old. The associations
were always almost in the same direction and not that robust,
not that impressive. There's also a gene. It has multiple
different forms, and the risk form is called apo E four.
(14:31):
That's the risk allele, and it really is especially a
risk factor for women's risk of developing Alzheimer's disease. And
when we looked at women who carried this risk alile,
then the associations were even more robust. So when I
started looking at started educating myself with regards to these
(14:55):
molecules and what they do, every single paper that I found,
every single one without exception, was on pre clamsia, this
condition that is deadly for women. They spontaneously develop hypertension,
high blood pressure, headache, strokes, and they could die if
intervention is not childmove from childbirth during pregnancy, it's later
(15:15):
stages of pregnancy. And so I thought, isn't this fascinating?
There is something about this biology that is specifically female.
So even if I didn't care about women's risk o baby,
which I did, the data really brought us into that realm.
And we started talking to obgyn specialists to understand hormones.
(15:38):
What's actually happening during pregnancy? Do we even understand And
the answer was, we don't even understand why women develop
pre clumsia. We still can't predict that. We don't understand it,
but we know some things about what we could go after.
Speaker 1 (15:53):
I think what's amazing is that we kind of assume
that people have got this, you know that like people
thought about this in the past. It's been studying women's
brain health. Shouldn't be such a novel concept, but yet
here we are today, and I think it's amazing. We
talk about the lack of data sets, and we always
kind of joke that even male mice didn't have a
seat at the table because we weren't even using you know,
(16:13):
female mice and experiments until relatively recently. In fact, Fanny
was the first person to use female stem cells in
the research. So that's why I'm blowing and them yes please,
And that's been just an amazing discovery.
Speaker 3 (16:26):
NIH and other mainly ANIH funded this incredibly visionary initiative
to create stem cells to study neurodegenative diseases. You know,
you can't sample someone's brain, so you can take stem
cells from them and create a brain in a dish.
You can create blood vessels in a dish. You can
recreate a lot of different things, and as we go forward,
(16:49):
we can do more and more and this is really
a game changing tool. So I was very excited to
start using stem cells in this resource three hundred plus
lines is in with all sorts of mutations everything. It's
one Northern European man in their fifties who donated their
(17:09):
selves and there is no equivalent.
Speaker 2 (17:12):
There is no female line. That's it.
Speaker 3 (17:15):
Imagine all the discoveries. This is taking us back to
when we started using mice. Every single scientific discovery is
going to be one hundred percent valid for that individual
to a certain extent, generalizable and you can extrapolate it
to the rest of people who would share that genotype
and background, but really not helpful if you're stuttying sex
(17:36):
differences or women's specific risk of all zeimercy these But
what's maybe more mind blowing than that. And so thanks
to the funding that we were able to receive, we
created initially by serendipity, every line that I created was female.
Speaker 2 (17:52):
It was not planned.
Speaker 3 (17:54):
It was just like every donor that I had in
the research that I created line. And then I was like, well,
we're going to create a resource that we're going to
make available to the scientific community that's going to be female.
But what was absolutely mind blowing is that this is
for the studies of neudugantive diseases with Alzheimer's being the
most common, and no one thought, shouldn't this be a
(18:16):
female line. If we're going to take one line, shouldn't
it be a female line. If we're going to go
after Alzheimer's disease as our goal. That's just mind blowing.
Speaker 1 (18:24):
We're at this critical moment where we have women's scientists
at this level who are discovering things in a moment
where it literally could change you know, the people in
this room. Our lives could be very different because of
the work that Doctorali is doing. And I really have
to thank you for the tireless work because I know,
with two young daughters and unbelievable long nights in the
(18:46):
lab and an obsession to solve this for all of us,
it's really remarkable to know you and to know your work.
Tell us about the IRB approvals that you recently got, well, I.
Speaker 3 (18:56):
Think the timing is really fascinating, right, because we've been
struggling with the ir BE.
Speaker 2 (19:00):
This is a regulatory.
Speaker 3 (19:01):
Approval to bring in human subjects and collect the data.
Speaker 2 (19:05):
I'm not kidding you.
Speaker 3 (19:07):
It's been just one thing after another, reversing and going back.
So I was almost ready to say, let's put a
pause on this, let's move on with the other projects
and come back.
Speaker 2 (19:17):
But we got approval last week. This is the mind menopause, menopause,
Mind matter.
Speaker 1 (19:26):
Menopause mind matter study. Yeah, and what's so exciting about
this is this is one of the first studies that's
going to really triangulate between brain health and women's sex differences.
And so again she's been waiting for months for approval,
got the funding, just recently got the initial funding at least,
just got the approval for this study, and is limited
(19:47):
to one hundred people to be part of this through perimenopause, menopause,
and postmenopause.
Speaker 3 (19:54):
Right, So every question that we start asking, we try
to access worldwide data whatever is available to us. That's
the fast this way. Then we use that data to
design experiments. But in this case, there was no data
to be accessed because again most of these large data
sets that have good phenotyping of the brain is sixty
five and above.
Speaker 2 (20:13):
So we don't actually.
Speaker 3 (20:14):
Know what that period in women's life where there's this
massive transition and hormonal states do, what the relationship between
that and the brain outcomes, namely Alzheimer's disease is, and
what role do hormones play And the reason why we
(20:34):
were really interested in hormones is that you can actually
intervene on that.
Speaker 2 (20:37):
So if we can understand which hormones in what combination,
in what dosage, and now that we have these blood
readouts of disease, we can really start asking these questions
in human beings as opposed to mice, rats and models,
and then understand how to intervene go back to those
(20:59):
models and see what you can actually change some of
the pathology. So that's why we needed to create this cord.
Speaker 3 (21:04):
And we hope that one hundred is not enough, but
this is what we can start with, and we really
hope that we can create this resource not just for
our own questions, but for the world to come and
ask very specific questions with regards to women's brain aging trajectory.
Speaker 1 (21:20):
The last thing I wanted to just ask you while
I have you, since we're talking about women's health and longevity,
what can you do? What can you do at any
age to expand your lifespan to health span? What are
the practices, the daily practices that can help each of
us right now as we're thinking about our brain health.
Speaker 3 (21:35):
I always used to start by saying exercise. It's true,
and we'll come back to that. But I want to
see reduce stress, and by that I mean reduce bad stress.
Not the stress that gets you activated and successful in life,
the stress where you feel trapped and helpless. I think
that kind of stress, aggressively lowering it through building the
(21:59):
community and support. But I want to come back to
exercise because that's a way to build it actually and
to counter this bad stress. So why exercise is the
single most important health measure across diseases, especially brain But
I think across diseases is not understood, and there are
(22:21):
a lot of great friends of mine who are trying
to discover the molecules and bottle it because that would
be the blockbuster. I mean, that just would be the
Nobel laureate unanimously. We don't want to exercise all the time.
I exercise, but every single time I would rather do
something else every single time. And I always envy those
(22:44):
who enjoy exercise so much that they need to get
pulled out of the gym.
Speaker 2 (22:48):
That's not me.
Speaker 3 (22:50):
So I don't know what it does, but it's more
than just molecules. I mean some of the things we
know bones are incredibly important for the brain. And so
when you're actually exercising, so strength training, not just cardiovascular exercise,
but strength training, when your muscles are sort of pulling
on the bone, there's a lot of action in the
bones that impacts the brain almost quite directly. You know,
(23:14):
biology is not as fixed as we used to think
about it, and so there's this like rebooting. It's almost
doing a little bit of violence to yourself, right, And
we know through epidemiological studies that when infections were around
and we were less sterile, we also did better with
regards to cardiovascular disease.
Speaker 2 (23:33):
And so this sort of sterile.
Speaker 3 (23:35):
Stressful environment is not good for our organs, including the brain.
So if you took someone's blood right after exercise, inflammation
markers are really high. But in the long run your
inflammation comes down. But the long run, you reset your
physiology and is a much healthier physiology. So exercise, exercise, exercise, exercise,
(24:00):
but strength training and then sleep and that's harder. But
if you do have control over some factors for your sleep,
control them sleep hyrogen, you know, not stressful things right
before going to bed where they can wake you up
in the middle of the night or keep you going,
so sleep hyrogen and being able to control what you
(24:20):
can control is important. Sleep apnea getting tested for that.
You could be incredibly thin and fit and have sleep apnia.
So if you're waking up in the middle of the
night or you don't feel refreshed, get tested for your sleep.
Diet is more complicated, but I think the principles of
avoiding simple sugars and carbohydrate and the Mediterranean like diet
(24:44):
is probably works. Vegetarian diet if you can do it
really well, which is hard, and you're not lacking in
nutrients and vitamins, could be helpful. So I think diet,
the jury is still out and I don't give any
dietary advice beyond avoid sugar.
Speaker 2 (25:02):
Alcohol. I don't think anyone thinks is good for your brain.
Speaker 3 (25:05):
But for my patients whose lifestyle is really linked to
that one glass of wine, I don't take it away
from them because I don't think we have enough data
on that. But I think each individual knows what's good
for them. Smoking is clearly not good for everyone or anyone, right,
and there's a lot of controversy with regards to fat
(25:26):
in general, so I don't think we understand it very well.
I think cholesterol and lipids have a very complicated biology
and not all of.
Speaker 2 (25:35):
It is what you actually eat.
Speaker 3 (25:38):
And I don't think anyone is like deep frying food
every day and eating them.
Speaker 1 (25:42):
But if you are, probably don't want to do that.
But you don't want to do the idea of my
brain being in her hands makes me feel very good.
It makes me sleep really well at night.
Speaker 2 (25:53):
Thanks so much for doing it. Thank you, Katty.
Speaker 1 (25:58):
What an amazing and full conversation. Doctor Olahi is doing
work that can improve life for everyone. Here are my
top takeaways. First, Alzheimer's is a woman's health issue. Two
thirds of those affected are women, and it seems that
women's scientists like doctor Olahi will find a way to
conquer it by looking at women's specific biology and hormones
(26:20):
and by studying the connection between conditions like menopause and Alzheimer's. Second,
we're already seeing game changers in the detection of Alzheimer's. Previously,
an expensive and uncomfortable spinal tap was necessary for early detection. Now,
says doctor Olahi, blood based biomarker testing can find the
(26:40):
disease sooner, more cheaply, and less invasively. Hopefully leading to
diagnosis before things become irreversible. Lastly, while genetics plays some
part in the development of Alzheimer's, environment is a huge
factor That means we can lessen our risk for the
disease by managing stress, getting plenty of e X, your
size and sleep, and maintaining a healthy diet. Have a
(27:03):
great day. For more podcasts from iHeartRadio, check out the
iHeartRadio app, Apple Podcasts, or wherever you listen to your
favorite shows. Today's episode of Here's Something Good on women's
health and longevity was brought to you by p ANDNG,
maker of trusted brands like Tampax Always and Always Discreet,
and by Walgreens, the women's well being destination, supporting every
(27:26):
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