Glial vascular degeneration in CADASIL.
Thea Brennan-Krohn1, Stephen Salloway, Stephen Correia
1Departments of Pathology (Neuropathology), Neurology, Medicine, and Psychiatry and Human Behavior, Rhode Island Hospital, Butler Hospital, Veterans Affairs Medical Center, and Warren Alpert Medical School of Brown University, Providence, RI, USA.
Journal of Alzheimer'S Disease : JAD
|April 20, 2011
Summary
CADASIL, a genetic dementia, involves Notch 3 gene mutations. Research shows white matter and vessel degeneration, with reduced IGF receptors and AAH, impacting Notch signaling.
Area of Science:
- Neuroscience
- Genetics
- Vascular Biology
Background:
- CADASIL is a hereditary vascular dementia linked to Notch 3 gene mutations.
- The precise mechanisms driving vascular degeneration in CADASIL remain unclear.
Purpose of the Study:
- To investigate upstream Notch signaling pathway components in CADASIL.
- To characterize molecular changes in white matter and vessels in CADASIL brains.
Main Methods:
- Gene expression analysis (mRNA) of key signaling molecules (Notch 1, 3, IGF receptors, AAH) in cortex and white matter.
- Assessment of cell types (neurons, glia) and vascular markers (SMA, endothelin-1).
- Immunohistochemistry for SMA degeneration and ubiquitin in vessel walls.
Main Results:
- Reduced white matter mRNA levels of Notch 1, Notch 3, AAH, SMA, and IGF receptors in CADASIL.
- Decreased vascular expression of SMA, IGF receptors, Notch 1, and Notch 3.
- CADASIL brains showed reduced SMA and increased ubiquitin in white matter and meningeal vessel walls, with no cortical abnormalities.
Conclusions:
- Molecular abnormalities in CADASIL are primarily confined to white matter and its vasculature.
- Findings suggest CADASIL involves glial and vascular degeneration, with impaired IGF receptor and AAH expression affecting Notch signaling.
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