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Photo Credit: Liza Simonsson.
Scientific Frontline: Extended "At a Glance" Summary
The Core Concept: CADASIL is a hereditary condition caused by NOTCH3 gene variants that degenerate vascular smooth muscle cells, leading to strokes, white matter changes, and cognitive decline.
Key Distinction/Mechanism: Unlike general vascular descriptions, new research identifies a specific molecular cascade where small vessel pathology disrupts mitochondrial function and energy production in the hippocampus. This leads to impaired gamma oscillations—brain rhythms essential for memory—and triggers inflammatory immune responses via specialized microglia.
Major Frameworks/Components:
- Mitochondrial Dysfunction: Reduced respiratory complexes and ATP production in brain vessels and cells.
- Hippocampal Vulnerability: Structural changes to neurons and impaired gamma oscillations.
- Neurovascular Unit Disruption: Loss of vascular smooth muscle cells and accumulation of NOTCH3 proteins.
- Immune Response: Increased attachment of microglia to vessels, specifically a subgroup linked to metabolism and inflammation.


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