Kind: captions
Language: en
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Alzheimer's has been a puzzle for a long
time. You see, inside the brains of
patients with the disease are two types
of abnormally folded proteins. But no
one knows which one's responsible for
the devastating symptoms.
One is the buildup of amalloid into
plaques and the other is what we call
tangles that accumulate inside the nerve
cells.
Tangles are composed of a protein called
Tao. Think of Tao as part of the cell's
architecture which helps stabilize
neurons and allows them to communicate.
Yet in Alzheimer's disease, Tao clumps
into toxic tangles and neurons die.
For a long time, it wasn't clear if the
amaloid or Tao were responsible for
Alzheimer's disease because both of them
are hallmarks for disease. So which is
cause and which is effect? And for a
long long time amaloid looked like the
culprit. Other types of dementia like a
disease called PSP started providing
clues about Alzheimer's by turning the
focus on Tao.
PSP is caused by Tao. Every symptom that
a patient gets with PSP is driven by
where TOAO deposits in the brain. So
suddenly we could give meaning to the
TOAW protein. We learned that if you
have abnormal TOAO, you will get sick.
You will get sick with 100% certainty.
The implications were huge. Tangles, not
plaques, may be what's responsible for
ravaging the brains of patients with
Alzheimer's. Abnormal tow, even without
amalloid, could be deadly. But how does
it wreak its havoc? In a stunning
experiment, Mark Diamond exposed healthy
cells to corrupted towel and then used
an electron microscope to see what
happened. So here's a picture now of
these large accumulations of towel sort
of attacking the cell surface and the
cell has actually started to rearrange
itself to capture them and what we saw
was remarkable. The normal form of the
towel within a day or so converted to
the abnormal form inside the cell. The
bad towel then escaped and invaded a
neighboring cell just like a pathogen.
It spread from neuron to neuron finally
explained to diseases including
Alzheimer's.
All of a sudden we have a totally new
way of thinking about how to treat
Alzheimer's disease. Abnormal tow is the
target. We've got to get rid of the
towel.
And by comparing amalloid and tow scans
in the same person, one thing is quite
clear.
In Alzheimer's disease, people don't get
tangles spreading throughout their brain
unless they have amaloid. So currently
we think that amaloid pulls the trigger
and tow is the bullet that unfortunately
kills the nerve cells.
If you want to treat a patient who has
Alzheimer's disease right now, you have
to treat the tangles. You have to treat
the amaloid 10 years before. If you're
suffering from this disease right now,
you have to hit the tangles. The tangles
are killing the nerve cells. To stop the
spread of tangles, David Holtzman has
developed a drug or antibbody to target
tow as it moves between neurons and he's
tested it in mice. These mice develop
towel pathology starting at let's say
about 5 months of age. So we gave the
antibbody from 6 months of age all the
way to 9 months of age. A point at which
we knew that all the animals would have
a lot of towel pathology in their brain.
The initial results were unbelievable.
It was obvious to anyone looking at the
mouse's brains that in one group the
pathology was much less than in the
other. Look at the treated mouse on the
left compared to the untreated mouse
which has a hard time moving as the
tangles attack its brain. If Holtzman's
drug can stop the spread of towel, it
might just help in the development of a
therapy for Alzheimer's disease as well.
One step at a time though. First the
drug has to be tested on human patients.
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