Understanding Dementia MOOC
More than amyloid beta: tau tangles and genetics in
Alzheimer’s disease
Video Transcript - Module 1
[Description not needed: The visuals in this video only support what is spoken;
the visuals do not provide additional information.]
Distinguished Professor James Vickers
So the other pathological structure we know that's really important for
Alzheimer's disease is known as the neurofibrillary tangle. Now the amyloid
plaques, they occur outside nerve cells and between nerve cells, and they
grow and then you develop thousands and then millions of these plaques
inside your brain, whereas neurofibrillary tangles are something that happens
within nerve cells. So the interesting thing is that, like amyloid plaques, these
tangles are actually made up of a protein that you find normally in nerve cells,
and that's called the tau protein. And it undergoes, again, this abnormal
transformation as part of forming tangles and it's highly insoluble which
means we can't dissolve it very easily in acids or alkaline solutions. So, in fact,
once the nerve cell has died, when you have a tangle inside the nerve cell it
slowly withers and degenerates, and then when it's died this tangle is actually
left behind sitting inside the brain. And we refer to it as a tombstone or ghost
tangle because it marks the degeneration of the nerve cell.
But again, a really interesting pathological picture in the sense that here's
another protein, normal protein, that we find inside our nerve cells that
undergoes this transformation to form the tangle.
What we have is a diagram of what happens to nerve cells as they form these
neurofibrillary tangles. So, here’s our diagram of a nerve cell, there are its
processes, in the middle is the nucleus, which contains the genetic machinery,
and within the neuron is this fine meshwork, a lattice of proteins that form
filaments. And we refer to this filamentous skeleton as the...
Professor Anna King
…as the cytoskeleton. Which is something you're very interested in James.
Distinguished Professor James Vickers
So we've been studying the cytoskeleton of neurons for many years, maybe
decades, and this is the structure that gets transformed in Alzheimer's disease,
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
©2025 Wicking Dementia Research and Education Centre, University of Tasmania, Australia, ABN 30 764 374 782. CRICOS Provider Code 00586B. You may
print, download and store this document in unmodified form only for your own personal, non-commercial and educational use. You may not reproduce or
communicate any of this content without the permission of the copyright owner.
Video Transcript - Module 1 - More than amyloid beta: tau tangles and genetics in Alzheimer’s disease - Page 1 of 4
so it gets disrupted and displaced by the neurofibrillary tangle. As shown in
the rest of this movie is the cytoskeleton, it becomes affected by the
degenerative process of Alzheimer's disease. The tangle forms and then the
neuron withers over time. And so eventually what you end up [with] inside the
brains of somebody with Alzheimer's disease is a collection of plaques as well
as the distribution of these tangles. Some of those are still intracellular and
some of those are also extracellular like those tombstone or ghost tangles.
One of the structures, though, that gets affected very early on in the condition,
and is of particular interest in research in Alzheimer's disease, is a structure
known as the hippocampus. Now the hippocampus as shown in this diagram
is buried deep within the temporal lobes of the brain. You've got two of these
hippocampi, if you like, inside the brain. And what we know, again, in the very
early stages of the condition that Alzheimer's disease affects nerve cells within
the hippocampus and it really destroys the connections of the hippocampus
with the rest of the brain.
Professor Anna King
And the hippocampus has a special function that is associated with the
symptoms of Alzheimer's disease.
Distinguished Professor James Vickers
Yes, so the hippocampus in particular, has this role in developing new
memories. It's not where the memories reside but it's like sensory information
comes into the brain, again through multiple modalities, it's funnelled down
into the hippocampus where it's processed in a particular way, and then that
message is then transmitted back out to the cerebral cortex where it's
encoded as long-term memory. So if you have damage to the hippocampus
then you'll disrupt this ability to form new memories. So those tangles that
we've described, one of the very earliest places that they start to develop is in
the hippocampus.
But as the disease marches on, and it will march on, those tangles will again
spread from the temporal lobe, through the temporal lobe to the parietal lobe
and to the frontal cortex and again, that's when you'll start to see all those
other particular neurological signs.
When you get to the end stage of Alzheimer's disease, though, it's usual that a
person is not very responsive, not aware really of what's going on around them,
very difficult to communicate with and are often sitting in a chair or lying in a
bed all day, and we know that the disease continues to spread. So, in fact, it
starts to affect areas in the core regions of the brain and the brainstem that
actually regulate some of our core physical functions like our respiration rate,
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
©2025 Wicking Dementia Research and Education Centre, University of Tasmania, Australia, ABN 30 764 374 782. CRICOS Provider Code 00586B. You may
print, download and store this document in unmodified form only for your own personal, non-commercial and educational use. You may not reproduce or
communicate any of this content without the permission of the copyright owner.
Video Transcript - Module 1 - More than amyloid beta: tau tangles and genetics in Alzheimer’s disease - Page 2 of
4
heart rate and then aspects such as feeding, swallowing, etc. And that's where
you see some of those physical features of advanced Alzheimer's disease.
Professor Anna King
Right at the end of the disease.
Distinguished Professor James Vickers
That's exactly right. There's a lot of interest in genetic risk factors for
Alzheimer's disease and other conditions that will cause dementia. For
Alzheimer's disease we know that there are a number of gene mutations that
will actually cause the disease, not necessarily when you're very young, but
when you get into, particularly into your 50s and 60s, if you carry one of these
mutations then you are at very high risk of developing dementia.
Professor Anna King
And in fact if you have one of these mutations you are likely to get dementia at
an earlier stage.
Distinguished Professor James Vickers
That's right, yes. So younger onset dementia usually has a very strong genetic
influence, not all cases, but in many of those cases you can then track that
down to particular mutations.
And then also in the rest of the population there are other genetic risk factors.
Now these aren't mutations. These are just variations in normal human genes
that may influence our individual risk.
So, Anna, this is a summary slide. I know that you're familiar with this one as
well which was originally developed by John Morris at the Washington
University, which really describes the current state of play in terms of our
understanding of when these pathological changes happen inside the brain
and then their various clinical expression. So we know that there's this lengthy
preclinical phase where in fact amyloid plaques are building up inside the
brains of people. Now people might get concerned about that, but in fact
actually a lot of people die at advanced age without dementia with a lot of
amyloid plaques in their brain. So there's still a bit of research to go on to
determine if there might be some minor psychological changes that are
associated with those changes.
But what's really important is when the tangles start to form inside the brain
and the connections between nerve cells start to happen …
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
©2025 Wicking Dementia Research and Education Centre, University of Tasmania, Australia, ABN 30 764 374 782. CRICOS Provider Code 00586B. You may
print, download and store this document in unmodified form only for your own personal, non-commercial and educational use. You may not reproduce or
communicate any of this content without the permission of the copyright owner.
Video Transcript - Module 1 - More than amyloid beta: tau tangles and genetics in Alzheimer’s disease - Page 3 of
4
Professor Anna King
The synapses.
Distinguished Professor James Vickers
That's right. Yeah, so the synaptic connections between nerve cells start to
degenerate and as those accumulate and spread throughout the brain then
you're probably going to reach a threshold where you start to see the onset of
symptoms. After that, then again, all of this only gets worse over time as the
pathology continues to develop and spread to other parts of the brain and
eventually, you know we consider Alzheimer's disease to be really a terminal
condition and when it starts to affect areas of your brain to do with mobility,
swallowing, feeding and so forth, and that places you at high risk of death.
Professor Anna King
So, would it be important to try and work out whether we're starting to
develop these amyloid plaques inside our brains at early stages before we
actually get these symptoms?
Distinguished Professor James Vickers
Yes. So there's new imaging methods that they can use in living human beings
to visualise amyloid plaques and even some newer approaches to try and
visualise the tau changes and the tangles inside the brain. But the conundrum
that people have is, if you're say, in your 70s and you have some amyloid
plaques in your brain, the preclinical phase may continue for some time on. So
this preclinical phase may be 5 years, 10 years or 20 years, so knowing that
somebody's got plaques inside the brain doesn't necessarily mean that they
will develop dementia within their lifetime.
And then people are interested in other, what they call biomarkers of the
condition. So is there something that we can measure in a sample like cerebral
spinal fluid or in blood that might be more indicative, perhaps of some of
those neurodegenerative changes inside the brain such as the tangles being
formed or the loss of synapses?
[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
©2025 Wicking Dementia Research and Education Centre, University of Tasmania, Australia, ABN 30 764 374 782. CRICOS Provider Code 00586B. You may
print, download and store this document in unmodified form only for your own personal, non-commercial and educational use. You may not reproduce or
communicate any of this content without the permission of the copyright owner.
Video Transcript - Module 1 - More than amyloid beta: tau tangles and genetics in Alzheimer’s disease - Page 4 of
4