Understanding Dementia MOOC
How does the brain change in Alzheimer’s disease?
Video Transcript - Module 1
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Professor Anna King
So all of these changes that can occur to a person, all of these symptoms that
can occur in a person who develops Alzheimer's disease, occur because there
are changes in specific regions of the brain. What sort of changes could we
expect to see in the brain of a person with Alzheimer's disease?
Distinguished Professor James Vickers
Certainly. So I guess one of the interesting things about Alzheimer's disease is
it tends to rob you of all of these higher brain functions. And many of these are
locked up in mysterious ways in the highest order areas of the brain, and in
particular, the cerebral cortex.
Professor Anna King
So that's this bit on the outside here of the brain.
Distinguished Professor James Vickers
That's right, and it looks sort of like this sort of scrunched up creature, mainly
because it's actually a big, flat sheet of cells that has to fit inside your skull, and
so it has this sort of scrunched up look, and it creates these bumps and
grooves. And what we know in Alzheimer's disease that it's not all of the
cerebral cortex which is affected, but in fact it's very specific parts of this
cerebral cortex which become damaged. And when they become damaged,
what happens to the brain is that it starts to shrink, and we refer to this as
atrophy. And as mentioned, there are actually very specific parts of the brain
that are affected or go through this process of atrophy in the brain in
Alzheimer's disease, and this includes the frontal lobe, the parietal lobe and, in
particular, also the temporal lobe. And what we actually think that this
shrinkage reflects the gradual progression of the disease. So the temporal lobe
is actually affected relatively early on in the disease process, and it's almost as if
then the pathology spreads to different parts of the brain, including the
parietal cortex and the frontal cortex.
And just as an example, when you start to see damage or atrophy, which
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Video Transcript - Module 1 - How does the brain change in Alzheimer’s disease? - Page 1 of 4
means also the loss of nerve cells and connections in the frontal cortex, that's
when you'll see neurological deficits such as the problems in logical thinking
and planning and organising, and also in areas such as your working memory
as well.
Professor Anna King
So the parts of the brain that are responsible for these functions are the parts
that degenerate in the disease.
Distinguished Professor James Vickers
Exactly, yes. And it's also important to remember it's not just the functions that
are situated in those particular regions of the brain. We know that the
neocortex does all these wonderful things and gives us all these wondrous
human qualities. It's because these regions are interconnected with each
other. And it's as if in Alzheimer's disease these regions are damaged by the
pathology but also you start to lose the connections between these higher
order areas of the brain and sometimes we refer to Alzheimer's disease as
really a disconnection syndrome. Individually those parts of the brain are
affected and it does shrink but there are still nerve cells there, but they
become disconnected from these other parts of the brain.
Professor Anna King
So, the brain's not really talking … different parts of the brain are not really
talking to each other properly.
Distinguished Professor James Vickers
That's right. Yeah, yeah. That's what's happening at the sort of macroscopic
level. We also know in Alzheimer's disease there are two specific pathological
changes that happen inside the brain. So if we could come in with our
microscope and look inside the neocortex we would find the presence of these
pathological structures. And this is why it's called Alzheimer's disease because
Alois Alzheimer, a German neuropathologist, was the first one to correlate
dementia as a clinical syndrome with these specific pathological changes or
hallmarks of the condition.
Professor Anna King
And that was over 100 years ago now that these were first identified, weren't
they?
Distinguished Professor James Vickers
That's right. Yeah. So there are two types of pathological hallmarks that are
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Video Transcript - Module 1 - How does the brain change in Alzheimer’s disease? - Page 2 of 4
very specific, I suppose, to Alzheimer's disease. And again, if a pathologist was
to look inside the brain they would be going looking for these particular
histological changes.
Now, one of these is the beta amyloid plaques, and the really interesting thing
about these amyloid plaques is, well, firstly that they're abnormal. So in
younger people we wouldn't expect to see them inside their brain, but they're
actually made up of a protein that all of our brains are making all the time. And
this is known as beta amyloid and beta amyloid is actually a normal protein. It
has a normal function, we don't quite exactly understand what that might be,
some people think it might be important for synaptic transmission or the
communication of nerve cells with each other. But somehow through this
pathological process associated with Alzheimer's disease it undergoes a
transformation. So again, these little structures that you see here are the
individual beta amyloid proteins. They abnormally form long filaments. The
filaments themselves start to develop within the brain. They self-aggregate
with each other and form these plaque-like structures.
Professor Anna King
And normally the brain would just clear these proteins away, wouldn't it? But
for some reason in Alzheimer's disease, that we don't fully understand, that
they form these aggregates and form these clumps.
Distinguished Professor James Vickers
Yes, and we think that your brain may start to form these clumps or
aggregates many years before you get overt symptoms, perhaps even decades
as well. And it's like they build up inside your brain over time.
Professor Anna King
But in fact, many people might have these aggregates in their brain and not
have any changes in their cognitive function.
Distinguished Professor James Vickers
That's right, so it's not actually sufficient just to have amyloid plaques in your
brain. You need the other pathological change known as the neurofibrillary
tangle.
And what we think might happen in terms of, in Alzheimer's disease, as shown
in this animation, is here we have the nerve cells that are interconnected with
each other. And then when we have these plaques starting to form inside the
brain, as shown in red, is that they might disrupt these long processes or axons
and cause them to degenerate.
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Video Transcript - Module 1 - How does the brain change in Alzheimer’s disease? - Page 3 of 4
Professor Anna King
Yes. And you can see in that picture the neurons were firing and that can alter
the firing ability of the neurons.
Distinguished Professor James Vickers
Yes. So, again, this idea that you start to lose connectivity between neurons
and that might underlie the development of those major clinical features.
[End of transcript]
From the U nde r s t a n d i ng De m e n t i a M O O C m o o c . u t a s . e d u . a u
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Video Transcript - Module 1 - How does the brain change in Alzheimer’s disease? - Page 4 of 4