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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Histology of CAA
- Disruption of vascular smooth muscle
- Animal studies of CVR in CAA
- Vascular reactivity - stimuli
- Animal models
- Human studies of CVR in CAA
- BOLD fMRI responses to visual stimulation
- Greater area of reduced BOLD amplitude in CAA
- CVR is reduced in presymptomatic CAA
- CVR decreases early in the disease course in CAA
- CVR decreases in the symptomatic phase of CAA
- Despite decreased CVR, resting perfusion is normal in CAA
- Decreased CVR is not caused by decreased neuronal electrical activity
- Measuring CVR across the whole brain
- CVR impairment is predominantly posterior
- Correlations between CVR, ischemia, hemorrhage and cognition
- Lower fMRI response is associated with more CMBs and WMH
- Lower CVR correlates with lower cognition
- CVR mediates part of the effect of CAA on cognition
- Putting it all together role of decreased CVR in CAA
- Can CVR be restored in CAA?
- Other unknowns
- Summary
- Disclosures and acknowledgements
Topics Covered
- Effects of CAA on the vessel wall
- Animal studies of cerebrovascular reactivity (CVR) in CAA
- Human studies of CVR in CAA
- Clinical correlates of loss of vascular reactivity
- Restoring CVR in CAA
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Smith, E.E. (2023, November 30). Vascular reactivity in cerebral amyloid angiopathy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 26, 2024, from https://doi.org/10.69645/HWNW4440.Export Citation (RIS)
Publication History
Financial Disclosures
- Commercial/Financial matters disclosed are consulting for Alnylam and Eli Lilly.
Other Talks in the Series: Cerebral Amyloid Angiopathy (CAA)
Transcript
Please wait while the transcript is being prepared...
0:00
Thank you for
watching this talk on
vascular reactivity in
cerebral amyloid angiopathy.
My name is Eric Smith,
I'm a Professor of Neurology
at the University of Calgary,
and the Kathy Taylor Chair
in Vascular Dementia.
0:15
In this talk, I will discuss
the effects of cerebral
amyloid angiopathy
or CAA on the vessel wall.
Review animal studies of
cerebrovascular reactivity,
abbreviated CVR, in CAA.
Then, I'll move on to
discuss the results of
human studies and the clinical
correlates of loss of CVR
and finally, address the
question of whether CVR
can be restored and with
what clinical benefits.
0:39
CAA is a small vessel disease
marked by the deposition of
beta-amyloid in the media and
adventitia of small arteries
in the cerebral cortex
and leptomeninges.
This deposition leads
to the thickening of
the vessel wall as
shown in the H&E stain.
There's also the
replacement of elements of
the vessel wall,
including loss of
smooth muscle cells as
they are replaced by
beta-amyloid as demonstrated
in the panel in the middle,
which shows the
characteristic apple-green
birefringence when
viewing the vessel.
Stained with congo red
under polarized light
and this reflects the
replacement of much of
the vessel wall by abeta
shown in the immunostain
in the vessel
demonstrating a
small arterial that
is heavily affected by CAA.
1:27
These panels
demonstrate the effect
of vascular amyloid
deposition on
loss of smooth muscle cells in
data collected from
triple transgenic mouse,
where the Swedish, Dutch,
and Iowa amyloid
precursor protein
or APP mutations
have been induced.
This animal exhibits
extreme vascular deposition
of beta-amyloid at an early age,
as shown in the
panel on the right.
Where the bright areas
indicate areas where there is
vascular deposition
of the beta-amyloid
demonstrated by thio-S.
The Panel on the left,
the remaining
smooth muscle cells
appear as the bright bands.
You can appreciate
those areas of
more severe amyloid
depositions are
marked by fewer
smooth muscle cells,
while the areas where there
is relative sparing of
amyloid deposition
have a larger number
of remaining smooth
muscle cells.
Because the smooth
muscle cells are
the contractile element
within the arterials,
one would expect that
lots of these cells
would be resulting
in a loss of CVR.
I'll then move on
to animal studies