Deposition of collagen IV and aggrecan in leptomeningeal arteries of hereditary brain haemorrhage with amyloidosis.

• Published in: Brain Research
• Main Authors: Snorradottir, Asbjorg Osk, Isaksson, Helgi J, Kaeser, Stephan A, Skodras, Angelos A, Olafsson, Elias, Palsdottir, Astridur, Bragason, Birkir Thor
• Other Authors: Univ Iceland, Inst Expt Pathol Keldur, IS-112 Reykjavik, Iceland, Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland, Univ Tubingen, Hertie Inst Clin Brain Res, Dept Cellular Neurol, Tubingen, Germany, German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany, Univ Iceland, Fac Med, IS-112 Reykjavik, Iceland, Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier Science BV 2014
• Subjects: Heilablóðfall; Stökkbreytingar; Frumur; Heilinn; Fullorðnir; Adult; Aged; 80 and over; Aggrecans; Amyloidosis; Brain; Cerebral Hemorrhage; Collagen Type IV; Cystatin C; Female; Humans; Male; Middle Aged; Mutation; Iceland
• Online Access: http://hdl.handle.net/2336/322354; https://doi.org/10.1016/j.brainres.2013.08.029

To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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. Icelandic Centre for Research (RANNIS) University of Iceland Research Fund Icelandic Centre for Research - Student's Innovation Fund Heilavernd fund Memorial fund of Hafdis Kjartansdottir Memorial fund of Helga Jonsdottir and Sigurlidi Kristjansson