TY - JOUR
T1 - Parenchymal cystatin C focal deposits and glial scar formation around brain arteries in Hereditary Cystatin C Amyloid Angiopathy.
AU - Osk Snorradottir, Asbjorg
AU - Isaksson, Helgi J
AU - Kaeser, Stephan A
AU - Skodras, Angelos A
AU - Olafsson, Elias
AU - Palsdottir, Astridur
AU - Thor Bragason, Birkir
AU - Snorradóttir, Ásbjörg Ósk
N1 - Funding Information:
This work was supported by grants from the Icelandic Centre for Research (RANNÍS) , the University of Iceland Research Fund , the Memorial fund of Hafdis Kjartansdottir , the Memorial fund of Helga Jonsdottir and Sigurlidi Kristjansson , and the Heilavernd fund . We would like to thank S. Arnadottir and M. Jonsdottir for technical assistance and our collaborators at the Department of Pathology, Landspitali National University Hospital, Iceland.
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/10/5
Y1 - 2015/10/5
N2 - 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.
AB - 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.
KW - Cystatin C distribution
KW - Focal deposits
KW - Glial scar
KW - Hereditary Cystatin C Amyloid Angiopathy
KW - Neuroinflammation
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:26115583&KeyUID=MEDLINE:26115583
UR - http://www.scopus.com/inward/record.url?scp=84940909091&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2015.06.019
DO - 10.1016/j.brainres.2015.06.019
M3 - Grein
C2 - 26115583
SN - 0006-8993
VL - 1622
SP - 149
EP - 162
JO - Brain Research
JF - Brain Research
ER -