1. Deposition of collagen IV and aggrecan in leptomeningeal arteries of hereditary brain haemorrhage with amyloidosis
- Author
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Stephan A. Kaeser, Astridur Palsdottir, Birkir Thor Bragason, Helgi J Isaksson, Angelos Skodras, Elias Olafsson, and Asbjorg Osk Snorradottir
- Subjects
Adult ,Male ,Collagen Type IV ,Pathology ,medicine.medical_specialty ,genetics [Amyloidosis] ,genetics [Cerebral Hemorrhage] ,Amyloid ,Cerebral arteries ,metabolism [Collagen Type IV] ,metabolism [Aggrecans] ,Laminin ,pathology [Brain] ,medicine ,Humans ,ddc:610 ,Aggrecans ,Cystatin C ,Molecular Biology ,Aggrecan ,metabolism [Cerebral Hemorrhage] ,Cerebral Hemorrhage ,Aged ,Aged, 80 and over ,metabolism [Amyloidosis] ,biology ,pathology [Cerebral Hemorrhage] ,business.industry ,General Neuroscience ,Amyloidosis ,Brain ,Middle Aged ,Hereditary cystatin C amyloid angiopathy ,medicine.disease ,genetics [Cystatin C] ,metabolism [Brain] ,Mutation ,biology.protein ,metabolism [Cystatin C] ,Female ,Neurology (clinical) ,Cerebral amyloid angiopathy ,pathology [Amyloidosis] ,business ,Developmental Biology - Abstract
Hereditary Cystatin C Amyloid Angiopathy (HCCAA) is a rare genetic disease in Icelandic families caused by a mutation in the cystatin C gene, CST3. HCCAA is classified as a cerebral amyloid angiopathy and mutant cystatin C forms amyloid deposits in cerebral arteries resulting in fatal haemorrhagic strokes in young adults. The aetiology of HCCAA pathology is not clear and there is, at present, no animal model of the disease. The aim of this study was to increase understanding of the cerebral vascular pathology of HCCAA patients with an emphasis on structural changes within the arterial wall of affected leptomeningeal arteries. Examination of post-mortem samples revealed extensive changes in the walls of affected arteries characterised by deposition of extracellular matrix constituents, notably collagen IV and the proteoglycan aggrecan. Other structural abnormalities were thickening of the laminin distribution, intimal thickening concomitant with a frayed elastic layer, and variable reduction in the integrity of endothelia. Our results show that excess deposition of extracellular matrix proteins in cerebral arteries of HCCAA is a prominent feature of the disease and may play an important role in its pathogenesis.
- Published
- 2013
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