TY - JOUR
T1 - Heparan sulfate proteoglycan expression in cerebrovascular amyloid β deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains
AU - Horssen, Jack
AU - Otte-Höller, Irene
AU - David, Guido
AU - Maat-Schieman, Marion L.
AU - Heuvel, Lambert P.
AU - Wesseling, Pieter
AU - Waal, Robert M.
AU - Verbeek, Marcel M.
PY - 2001
Y1 - 2001
N2 - Cerebrovascular deposition of amyloid β protein (Aβ) is a characteristic lesion of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Besides Aβ, several other proteins and proteoglycans accumulate in cerebral amyloid angiopathy (CAA). We have now analyzed the expression of the heparan sulfate proteoglycan (HSPG) subtypes agrin, perlecan, glypican-1, syndecans 1-3 and HS glycosaminoglycan (GAG) side chains in CAA in brains of patients with AD and HCHWA-D. Hereto, specific well-characterized antibodies directed against the core protein of these HSPGs and against the GAG side chains were used for immunostaining. Glypican-1 was abundantly expressed in CAA both in AD and HCHWA-D brains, whereas perlecan and syndecans-1 and -3 were absent in both. Colocalization of agrin with vascular Aβ was clearly observed in CAA in HCHWA-D brains, but only in a minority of the AD cases. Conversely, syndecan-2 was frequently associated with vascular Aβ in AD, but did not colocalize with vascular Aβ deposits in HCHWA-D. The three different syndecans, agrin, glypican-1 and HS GAG, but not perlecan, were associated with the majority of senile plaques (SPs) in all brains. Our results suggest a role for agrin in the formation of SPs and of CAA in HCHWA-D, but not in the pathogenesis of CAA in AD. Both syndecan-2 and glypican, but not perlecan, may be involved in the formation of CAA. We conclude that specific HSPG species may be involved in the pathogenesis of CAA in both AD and HCHWA-D, and that the pathogenesis of CAA and SPs may differ with regard to the involvement of HSPG species.
AB - Cerebrovascular deposition of amyloid β protein (Aβ) is a characteristic lesion of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Besides Aβ, several other proteins and proteoglycans accumulate in cerebral amyloid angiopathy (CAA). We have now analyzed the expression of the heparan sulfate proteoglycan (HSPG) subtypes agrin, perlecan, glypican-1, syndecans 1-3 and HS glycosaminoglycan (GAG) side chains in CAA in brains of patients with AD and HCHWA-D. Hereto, specific well-characterized antibodies directed against the core protein of these HSPGs and against the GAG side chains were used for immunostaining. Glypican-1 was abundantly expressed in CAA both in AD and HCHWA-D brains, whereas perlecan and syndecans-1 and -3 were absent in both. Colocalization of agrin with vascular Aβ was clearly observed in CAA in HCHWA-D brains, but only in a minority of the AD cases. Conversely, syndecan-2 was frequently associated with vascular Aβ in AD, but did not colocalize with vascular Aβ deposits in HCHWA-D. The three different syndecans, agrin, glypican-1 and HS GAG, but not perlecan, were associated with the majority of senile plaques (SPs) in all brains. Our results suggest a role for agrin in the formation of SPs and of CAA in HCHWA-D, but not in the pathogenesis of CAA in AD. Both syndecan-2 and glypican, but not perlecan, may be involved in the formation of CAA. We conclude that specific HSPG species may be involved in the pathogenesis of CAA in both AD and HCHWA-D, and that the pathogenesis of CAA and SPs may differ with regard to the involvement of HSPG species.
KW - Alzheimer's disease
KW - Amyloid β protein
KW - Cerebral amyloid angiopathy
KW - Heparan sulfate proteoglycans
KW - Hereditary cerebral hemorrhage with amyloidosis of the Dutch type
UR - http://www.scopus.com/inward/record.url?scp=0035157875&partnerID=8YFLogxK
U2 - 10.1007/s004010100414
DO - 10.1007/s004010100414
M3 - Article
C2 - 11761721
AN - SCOPUS:0035157875
SN - 0001-6322
VL - 102
SP - 604
EP - 614
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 6
ER -