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Updated: Jul 6, 2025
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
CADASIL: A NOTCH3-associated cerebral small vessel disease
Lamei Yuan1, Xiangyu Chen2, Joseph Jankovic3
1Health Management Center, the Third Xiangya Hospital, Central South University, Changsha, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China; Disease Genome Research Center, Central South University, Changsha, China; Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China.
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic small vessel disease caused by NOTCH3 mutations. This review explores CADASIL pathogenesis, diagnosis, and treatment, highlighting NOTCH3
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD).
- Pathologically, CADASIL involves a non-atherosclerotic, non-amyloid angiopathy affecting cerebral arteries.
- NOTCH3 gene mutations were identified as the cause in 1996, though other genetic CSVDs mimic the phenotype.
Purpose of the Study:
- To review current progress in CADASIL, focusing on clinical, neuroimaging, pathological, and genetic aspects.
- To provide insights into the pathogenesis, diagnosis, and personalized therapy of hereditary CSVDs.
- To highlight the role of NOTCH3 mutations in CADASIL and differential diagnoses.
Main Methods:
- Literature review of studies on CADASIL and other hereditary CSVDs.
- Synthesis of current knowledge on clinical presentation, neuroimaging findings, and pathology.
- Analysis of genetic factors, diagnostic criteria, and therapeutic strategies.
Main Results:
- NOTCH3 mutations are central to CADASIL, a well-recognized hereditary disorder.
- Other genetic CSVDs can present similarly, necessitating careful differential diagnosis.
- Understanding NOTCH3's role in pathogenesis remains an active area of research.
Conclusions:
- CADASIL is a distinct NOTCH3-associated CSVD, but shares features with other hereditary CSVDs.
- Comprehensive understanding of clinical, genetic, and pathological aspects is crucial for diagnosis and management.
- Further research is needed to elucidate the precise role of NOTCH3 in CADASIL pathogenesis.
Background:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of studies investigating this disease is increasing, the role of NOTCH3 in the pathogenesis of CADASIL remains elusive.
Aim Of Review:
This review aims to provide insights into the pathogenesis and the diagnosis of hereditary CSVDs, as well as personalized therapy, predictive approach, and targeted prevention. In this review, we summarize the current progress in CADASIL, including the clinical, neuroimaging, pathological, genetic, diagnostic, and therapeutic aspects, as well as differential diagnosis, in which the role of NOTCH3 mutations is highlighted.
Key Scientific Concepts Of Review:
In this review, CADASIL is revisited as a NOTCH3-associated CSVD along with other hereditary CSVDs.
