Brain Coffee Video Podcast Episode 9 – The State of Alzheimer’s Research

Brain Coffee Video Podcast Episode 9 – The State of Alzheimer’s Research


Welcome to the Brain Coffee Podcast, where
Doctors Eric Leuthardt and Albert Kim unlock life’s little mysteries about health, wellness,
entertainment, technology and how the brain makes sense of it all. Sit back, relax and open up your mind. Dr. Eric Leuthardt:
Well, David, thanks for joining us at Brain Coffee. Dr. Albert Kim:
Thank you very much, yeah. Dr. Eric Leuthardt:
It’s usually just the two of us king of yammering away. But again, it’s a real pleasure to basically
have you here given your busy schedule and all the research that you do. So thanks very much. Dr. Albert Kim:
Yeah, thank you. Dr. David Michael Holtzman:
This is such a nice local place. This is awesome. Dr. Albert Kim:
It is a good place. Dr. Eric Leuthardt:
Well definitely, you know, the kolaches. Don’t forget to get a kolache before you
go. Dr. Albert Kim:
They’re good here. They’re filling. So why don’t we, no please. Dr. Eric Leuthardt:
You’re obviously a expert, you know, really one of the world-renowned experts in Alzheimer’s. At the highest level, could you give the briefest
summary of kind of, you know, where you think we are today when we think about Alzheimer’s? Dr. Albert Kim:
Yeah, the lay of the land. I think that would be useful. Dr. David Michael Holtzman:
You know, I think there’s been sort of a revolution in our understanding about Alzheimer’s
in the last 20 years, especially the last 10. We used to think of it as when people began
to develop memory loss and other changes, that that was the disease. And of course, those are the manifestations
of the disease, but it turns out, I think the biggest thing which is really important
for developing treatments, is that the disease starts in the brain about 20 years before
the symptoms start. Dr. Albert Kim:
Wow. Dr. David Michael Holtzman:
And because of that, I mean, that, and we can now detect those changes as they’re
occurring with different tests. And So I think it’s setting the stage where
now there are actually trials of new treatments in people that are normal, cognitively normal,
who have the manifestations of the disease in the brain, so that we can actually try
to delay the disease or prevent it. And that, that’s really huge. Now there’s nothing yet that we have that’s
approved, but I think that’s where really things are moving. Dr. Eric Leuthardt:
So what are the things that you can see 20 years before anything clinical happens? Dr. David Michael Holtzman:
The first things we can see at least by some imaging techniques and by looking at the spinal
fluid, is that amyloid. This protein that normally is made by all
of us, which is floating around. It starts to clump up. And you can see that beginning about 20 years
before symptoms. Dr. Albert Kim:
I see. Dr. David Michael Holtzman:
It starts to build up. Dr. Eric Leuthardt:
Now this amyloid protein, is it, I’m again, you know more about this than I do, but amyloid
is really kind of almost like the output of like neurons being busy, right? Like, so as neurons are active, they produce
amyloid naturally, right? Dr. David Michael Holtzman:
They produce it naturally, except it’s in a state where it’s just freely soluble,
meaning it’s like dissolving sugar in your coffee. It dissolves, right? But when the disease starts, it comes out
of solution and clumps up. And so it’s a different conformation of— Dr. Albert Kim:
I see. Dr. David Michael Holtzman:
It’s totally; same sequence, but a different conformation. Dr. Eric Leuthardt:
Very interesting. Dr. Eric Leuthardt:
My causal way of thinking about it, I kind of think of it as neuron poop. You know what I mean? Like, you know, and basically that like, basically
your neurons poop. They poop out the amyloid. And just, you know, for whatever reason, you
can’t flush the toilet anymore. Dr. David Michael Holtzman:
And then the toilet gets stuck and you can’t clear it out. Dr. Eric Leuthardt:
Exactly. It gets kind of stinky. Dr. Albert Kim:
But the poop is different, you’re saying. Dr. Eric Leuthardt:
Right, the poop changing. Dr. David Michael Holtzman:
Right, right. Dr. Albert Kim:
It’s not that normal poop. Dr. David Michael Holtzman:
Right, right, that’s right. It’s a little different. Dr. Albert Kim:
Do you see this in other disorders? This stuff glomming up the brain? Dr. David Michael Holtzman:
The same amyloid protein builds up in Alzheimer’s disease. But it also accumulates in a related condition
where it builds up in the blood vessels. Amyloid angiopathy. Dr. Albert Kim:
Right, right, right. Dr. David Michael Holtzman:
And that is a, you guys see in your practices. I mean, it causes hemorrhages. (CROSS-TALK) Dr. Albert Kim:
I see. Dr. David Michael Holtzman:
But there are other amyloids, other sequences of proteins that form what we call an amyloid
structure, that also affect brain. They’re less common. And, of course, this occurs, amyloidosis occurs
systemically, this systemic amyloidosis. And that is where things build up in the heart
or the kidney, right? And that, those are pretty common. Dr. Eric Leuthardt:
That’s interesting. Dr. Albert Kim:
I see. Dr. David Michael Holtzman:
Sometimes in the nerve. Dr. Eric Leuthardt:
Is there a relationship between amyloid and depression? Because I’ve recently heard that people
are starting to treat Alzheimer’s with antidepressant drugs. Dr. David Michael Holtzman:
There’s sort of two things with depression. One is that a fair number of people will begin
to develop depression as their first manifestation of disease. Dr. Albert Kim:
Oh, I see. Dr. David Michael Holtzman:
That’s one thing. But, the other thing that’s been found by
people at Wash U actually, is that some antidepressants lower the production of amyloid in the brain. Dr. Albert Kim:
Oh, that’s interesting. So it might, it might get at the cause of
it as well, to some extent. Dr. David Michael Holtzman:
Correct, right. So one of the main treatments being developed
are things that inhibit the production of amyloid in a very specific way. What turns out, some antidepressants do the
same thing. Not as strong as a specific inhibitor, but. Dr. Eric Leuthardt:
Oh, that’s really interesting. Now, but again, amyloid is, you know, again,
I think we’ve been totally interrupting him. We should probably let the expert speak. Dr. Albert Kim:
Oh, yeah, oh no, apologize. Dr. Eric Leuthardt:
But you know, amyloid is I guess, one part of the protein story, right? Like you know, I guess there’s also Tau. And everybody loves to talk about Tau as it
relates to sports injuries and stuff like that. Dr. Albert Kim:
Right, right, CTE. Dr. David Michael Holtzman:
One way, I’ve heard a lot of people give the analogy that amyloid kind of is the, is
the gun of Alzheimer’s disease. It starts the whole thing. And that Tau is the bullet that actually is
causing the damage. And I think there’s a lot of, there’s
strong evidence that that’s the case. Now that we have neuroimaging that you can
see Tau accumulating, in the last two, three years, we’ve been able to see that as, wherever
Tau is building up the poop of the brain. Another kind of poop. Wherever Tau is accumulating, that’s where
the symptoms are. Dr. Eric Leuthardt:
Uh-huh. Dr. David Michael Holtzman:
So if it starts in the part of the brain that controls memory, you get memory loss. As it spreads to other areas that affect language,
then you get language abnormalities. It’s really, really compelling. Dr. Albert Kim:
Wow. Dr. David Michael Holtzman:
And the brain shrinks in the areas that Tau accumulates. So it really is the damaging molecule of the
disease. Dr. Albert Kim:
I see. It’s the most, well, what’s the relationship
between the beta amyloid and the Tau then? How do they communicate with each other? Dr. David Michael Holtzman:
So there’s two things. One is that, we know from lots of studies,
that amyloid causes the Tau pathology to get a lot worse. It drives it. What we don’t know is, how it does that. So a lot of researchers are now trying to
figure out how is amyloid interacting with Tau. Dr. Albert Kim:
I see. Dr. Eric Leuthardt:
Maybe even a bigger blue sky question is, let’s say we can reduce beta amyloid, once
the damage is done, is it reversible? Dr. David Michael Holtzman:
No one knows. I hope, I hope it is, but I think it’s much
more realistic to think if you hit it before the damage is done, that that’s where you’re
really going to have a big impact. This is like, I think of a lot like atherosclerosis. Huge decreases in heart attacks and strokes
because now our choles-, we can lower our cholesterol, we can control our blood pressure. And we have markers. You know, you measure your cholesterol. If it’s too high, you get on a statin or
you exercise more or you do other things. Same thing I think will be for this. I don’t think, you know, we’re going to
probably have to diagnose it before you’re symptomatic, and start getting on the treatments
that, you know, prevent the build-up from getting worse. Dr. Albert Kim:
I see. This is just my sci-fi mind going into overdrive. You know, there’s these researchers, again,
in the brain-computer interface space making what are called hippocampal chips. Have you heard about these things? Dr. David Michael Holtzman:
No, no, no I haven’t heard of those. Dr. Eric Leuthardt:
So at USC, they now have a replacement for a mouse hippocampus, where basically, quite
literally, you put this, you put the wires and they remove a portion of the hippocampus. They put wires in one side and wires in the
other side. And they have the signals go to this chip. And then basically, it allows for restoration
of memories for that— Dr. David Michael Holtzman:
Oh, wow. Dr. Eric Leuthardt:
For that mouse. Dr. Albert Kim:
Oh, that’s interesting. Dr. Eric Leuthardt:
It’s this guy, Ted Berger. And he really does some amazing stuff. Dr. David Michael Holtzman:
That’s a cool idea. Because you’d think higher order processing
is not through the hippocampus. That’s just, it’s just a conduit to allow
things like memory to happen, other things. Dr. Eric Leuthardt:
That’s right, yeah, yeah, yeah. Dr. David Michael Holtzman:
So if you could replace that conduit. Dr. Eric Leuthardt:
Yeah, so there is; and they have these mouse demonstrations that it’s possible. So that’s why I was just going to just– Dr. Albert Kim:
That’s interesting. But the hippocampus is one of the parts of
the brain earliest affected, one of the earliest affected. Dr. David Michael Holtzman:
It’s one of the earlier affected areas. But one of the things I always like to, when
I see patients who have, are developing Alzheimer’s disease, memory is not the only thing affected. So it is certainly prominent early, but it’s
not the only thing. Even early on, you’ll almost always see
executive disfunction. So trouble would be like, multitasking issues. But yeah, no, it is certainly a prominent
early, early finding. Dr. Albert Kim:
I see.

1 thought on “Brain Coffee Video Podcast Episode 9 – The State of Alzheimer’s Research

  1. This is great podcast and I wasn't aware of this until we went to see BrainWorks at The Repertory Theater on July 20.I did research about BrainWorks and then found info on the podcasts. You should consider marketing this at the WU Clinics, online, radio, and TV. I will be watching the other previous podcasts. Thanks for getting the info out. The BrainWorks performance/production was great!

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