CADASIL: yesterday, today, tomorrow

Background and purpose In 2019, the Brain Prize crowned the discovery of CADASIL in the 1990s and research efforts on this archetypal small vessel disease of the brain over 40 years. Methods and results The hereditary origin of this arteriolopathy was discovered from a first clinical case and detail...

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Bibliographic Details
Published in:European journal of neurology 2020-08, Vol.27 (8), p.1588-1595
Main Authors: Chabriat, H., Joutel, A., Tournier‐Lasserve, E., Bousser, M. G.
Format: Article
Language:English
Subjects:
Animal diseases
Animal models
Blood vessels
Brain
CADASIL
cognitive disorders and dementia
Dementia disorders
Disease
Drug development
genetic and inherited disorders
Genetic screening
leukodystrophies
MRI brain lesions
Mutation
neurological disorders
NOTCH3 gene
Notch3 protein
Pathophysiology
Research projects
stroke cerebrovascular diseases and cerebral circulation
Vascular diseases
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Summary:Background and purpose In 2019, the Brain Prize crowned the discovery of CADASIL in the 1990s and research efforts on this archetypal small vessel disease of the brain over 40 years. Methods and results The hereditary origin of this arteriolopathy was discovered from a first clinical case and detailed observation of the patient’s family. Thereafter, the role of causative mutations within the NOTCH3 gene were identified, allowing the development of a genetic test and then of an animal model of the disease. These crucial steps led to the discovery progressively that CADASIL is the most common genetic cerebral small vessel disease, to describing for the first time the natural history of a cerebral ischaemic small vessel disease from silent cerebral tissue lesions up to severe motor disability and dementia at the end stage, to demonstrating the central role of matrix proteins in its pathophysiology and to opening the door to the discovery of several other genes involved in monogenic cerebral small vessel diseases. Discussion Today, CADASIL is known to every neurologist, but the disease has not yet revealed all its secrets. A lot of effort is still needed to understand the intimate mechanisms of the disease and the most efficient targets or approaches for the development of efficient therapeutics. The history of CADASIL will be further enriched by multiple ongoing research projects worldwide, at clinical and preclinical level, and will continue to enlighten research in the field of cerebral small vessel disorders.
ISSN:1351-5101
1468-1331
DOI:10.1111/ene.14293