CADASIL: yesterday, today, tomorrow

Area of Science:

• Neurology
• Genetics
• Pathophysiology

Background:

• CADASIL, an archetypal small vessel disease of the brain, has been researched for over 40 years.
• Recognized as the most common genetic cerebral small vessel disease.
• The Brain Prize in 2019 highlighted CADASIL research milestones.

Purpose of the Study:

• To review the discovery and research history of CADASIL.
• To highlight key findings in understanding CADASIL pathophysiology and genetics.
• To emphasize the ongoing need for therapeutic development.

Main Methods:

• Discovery through family studies of initial clinical cases.
• Identification of NOTCH3 gene mutations.
• Development of genetic testing and animal models.

Main Results:

• Established CADASIL as the most common genetic cerebral small vessel disease.
• Described the natural history from silent lesions to severe disability and dementia.
• Demonstrated the role of matrix proteins in pathophysiology.
• Facilitated discovery of other monogenic small vessel diseases.

Conclusions:

• CADASIL is widely recognized, but its mechanisms require further elucidation.
• Understanding disease mechanisms is crucial for developing effective therapeutics.
• Ongoing global research will advance CADASIL knowledge and cerebral small vessel disorder research.