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Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families
N J Thomas1, C M Morris, F Scaravilli
1Institute for the Health of the Elderly, University of Newcastle, Newcastle upon Tyne, United Kingdom.
Insights
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic artery disorder causing dementia. Research aims to understand its link to NOTCH 3 gene mutations and brain cell effects.
Area of Science:
- Neurology
- Genetics
- Vascular Biology
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common inherited vascular dementia.
- Previously considered a familial Binswanger disease, CADASIL is distinct as it does not involve hypertension or cardiovascular risk factors.
Purpose of the Study:
- To investigate the genetic basis and pathogenesis of CADASIL.
- To explore the microvascular pathology in CADASIL to differentiate genetic effects from systemic vascular influences.
Main Methods:
- Genetic analysis focusing on NOTCH 3 gene mutations.
- Examination of microvascular pathology in affected individuals.
Main Results:
- CADASIL is linked to single missense mutations in the NOTCH 3 gene on chromosome 19.
- The specific genetic mechanisms leading to brain infarcts and dementia remain unknown.
Conclusions:
- CADASIL is a primary arterial disorder caused by NOTCH 3 gene mutations.
- Further research into microvascular pathology is crucial for understanding the disease's pathogenesis and its impact on brain cells.
Abstract:
The most common form of familial vascular dementia is considered to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is now also increasingly manifest in the United Kingdom. CADASIL has been previously dubbed as a familial form of Binswanger disease. However, unlike in Binswanger disease CADASIL does not involve hypertension or other risk factors associated with cardiovascular disease. CADASIL appears to be essentially a disorder of the arteries that is linked to single missense mutations in the NOTCH 3 gene locus on chromosome 19. The pathogenesis of the disorder or the genetic mechanism leading to brain infarcts and dementia is not known. The elucidation of the microvascular pathology evident in CADASIL may be an interesting way to delineate effects of defective genes on brain cells from systemic vascular influences.