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CADASIL

new advances in basic science and clinical perspectives

Ferrante, Elisa A.; Cudrici, Cornelia D.; Boehm, Manfred

Current Opinion in Hematology: May 2019 - Volume 26 - Issue 3 - p 193–198
doi: 10.1097/MOH.0000000000000497
VASCULAR BIOLOGY: Edited by M. Luisa Iruela-Arispe
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Purpose of review Recent advances in genetic evaluation improved the identification of several variants in the NOTCH3 gene causing Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Despite improved diagnosis, the disease mechanism remains an elusive target and an increasing number of scientific/clinical groups are investigating CADASIL to better understand it. The purpose of this review is to summarize the current knowledge in CADASIL.

Recent findings CADASIL is a genotypically and phenotypically diverse condition involving multiple molecular systems affecting small blood vessels. Cerebral white matter changes observed by MRI are a key CADASIL characteristic in young adult patients often before severe symptoms and trigger NOTCH3 genetic testing. NOTCH3 mutation locations are highly variable, correlate to disease severity and consistently affect the cysteine balance within extracellular Notch3. Granular osmiophilic material deposits around blood vessels are also a unique CADASIL feature and appear to have a role in sequestering proteins that are essential for blood vessel homeostasis. As potential biomarkers and therapeutic targets are being actively investigated, neurofilament light chain can be detected in patient serum and may be a promising circulating biomarker.

Summary CADASIL is a complex, devastating disease with unknown mechanism and no treatment options. As we increase our understanding of CADASIL, translational research bridging basic science and clinical findings needs to drive biomarker and therapeutic target discovery.

National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to Elisa A. Ferrante, PhD, National Institutes of Health, 10 Center Drive, Bldg 10-CRC 5E-3256, Bethesda, MD 20892, USA. Tel: +1 301 402 3577; e-mail: elisa.ferrante@nih.gov

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