CADASIL: The Most Common Hereditary Subcortical Vascular Dementia

Hannu Kalimoa Department of Pathology, University & University Hospital of Helsinki, Helsinki, Finland and, Uppsala University, Uppsala, Sweden and, Departments of Pathology & Forensic Medicine, Turku University & University Hospital, Turku, Finland. Tel.: +358 919 126 882 +358 504 270 836 Fax: +358 919 126 [email protected]Correspondence[email protected]

Qing Miaob Department of Pathology, Turku University, Turku, Finland. Tel.: +358 2333 7315 Fax: +358 2333 [email protected]

Saara Tikkac Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland and, Department of Pathology, Helsinki University, Helsinki, Finland. Tel.: +358 919 125 203 Fax: +358 219 125 [email protected]

Kati Mykkänend Department of Medical Biochemistry & Genetics, University of Turku, Turku, Finland. Tel.: +358 2333 7456 Fax: +358 2333 [email protected]

Maija Junnae Department of Medical Biochemistry & Genetics, University of Turku, Turku, Finland. Tel.: +358 2333 7456 Fax: +358 2333 [email protected]

Susanna Roinef Department of Neurology, University Hospital of Turku, Turku, Finland. Tel.: +358 2313 0715 Fax: +358 2313 [email protected]

Matti Viitaneng Division of Clinical Geriatrics, Karolinska Institutet & Karolinska University Hospital, Stockholm, Sweden and, Department of Geriatric Medicine, University of Turku, Turku, Finland. Tel.: +358 2269 1996 Fax: +358 2269 [email protected]

Minna Pöyhönenh Department of Medical Genetics, University of Helsinki, Helsinki, Finland and, Department of Clinical Genetics, Helsinki University Hospital, Helsinki, Finland. Tel.: +358 919 125 091 Fax: +358 919 125 [email protected]

Marc Baumanni Protein Chemistry Unit, Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland. Tel.: +358 919 125 200 Fax: +358 219 125 [email protected]

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Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is the most common hereditary subcortical vascular dementia. It is caused by the defective NOTCH3 gene, which encodes a transmembrane receptor; over 170 different mutations are known. The main clinical features are migraine with aura (often atypical or isolated), strokes, cognitive decline/dementia and psychiatric symptoms. Executive and organizing cognitive functions are impaired first, memory is affected late. Typical MRI findings are T2 weighted hyperintensities in temporopolar white matter and the capsula externa. Smooth muscle cells in small arteries throughout the body degenerate and vessel walls become fibrotic. In the brain, this results in circulatory disturbances and lacunar infarcts, mainly in cerebral white matter and deep gray matter. The exact pathogenesis is still open: a dominant-negative toxic effect is suggested, possibly related to Notch3 misfolding. Diagnosis is reached either by identifying a pathogenic NOTCH3 mutation or by electron microscopic demonstration of granular osmiophilic material in a (skin) biopsy. Only symptomatic treatment is available at present.

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The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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CADASIL: The Most Common Hereditary Subcortical Vascular Dementia

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CADASIL: The Most Common Hereditary Subcortical Vascular Dementia

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