Vascular reactivity in cerebral amyloid angiopathy

Published on November 30, 2023   20 min

Other Talks in the Series: Cerebral Amyloid Angiopathy (CAA)

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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

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Vascular reactivity in cerebral amyloid angiopathy

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