Parenchymal cystatin C focal deposits and glial scar formation around brain arteries in Hereditary Cystatin C Amyloid Angiopathy.

• Published in: Brain Research
• Main Authors: Osk Snorradottir, Asbjorg, Isaksson, Helgi J, Kaeser, Stephan A, Skodras, Angelos A, Olafsson, Elias, Palsdottir, Astridur, Thor Bragason, Birkir
• Other Authors: 1 Univ Iceland, Inst Expt Pathol, Keldur, IS-112 Reykjavik, Iceland 2 Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland 3 Univ Tubingen, Dept Cellular Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany 4 German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany 5 Univ Iceland, Fac Med, IS-112 Reykjavik, Iceland 6 Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland 7 Univ Iceland, Fac Med, Sch Hlth Sci, Biomed Ctr, IS-112 Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier Science BV 2015
• Subjects: Heilablóðfall; Arfgengi; Cystatin C/genetics; Cerebral Hemorrhage/genetics; Cerebral Amyloid Angiopathy; Iceland
• Online Access: http://hdl.handle.net/2336/581414; https://doi.org/10.1016/j.brainres.2015.06.019

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 an amyloid disorder in Icelandic families caused by an autosomal dominant mutation in the cystatin C gene. Mutant cystatin C forms amyloid deposits in brain arteries and arterioles which are associated with changes in the arterial wall structure, notably deposition of extracellular matrix proteins. In this post-mortem study we examined the neuroinflammatory response relative to the topographical distribution of cystatin C deposition, and associated haemorrhages, in the leptomeninges, cerebrum, cerebellum, thalamus, and midbrain of HCCAA patients. Cystatin C was deposited in all brain areas, grey and white matter alike, most prominently in arteries and arterioles; capillaries and veins were not, or minimally, affected. We also observed perivascular deposits and parenchymal focal deposits proximal to affected arteries. This study shows for the first time, that cystatin C does not exclusively form CAA and perivascular amyloid but also focal deposits in the brain parenchyma. Haemorrhages were observed in all patients and occurred in all brain areas, variable between patients. Microinfarcts were observed in 34.6% of patients. The neuroinflammatory response was limited to the close vicinity of affected arteries and perivascular as well as parenchymal focal deposits. Taken together with previously reported arterial accumulation of extracellular matrix proteins in HCCAA, our results indicate that the central nervous system pathology of HCCAA is characterised by the formation of a glial scar within and around affected arteries. Icelandic Centre for Research (RANNIS) University of Iceland Research Fund Memorial fund of Hafdis Kjartansdottir Memorial fund of Helga Jonsdottir and Sigurlidi Kristjansson Heilavemd fund