Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains

Cerebrovascular deposition of amyloid beta protein (A beta) is a characteri stic lesion of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Besides A beta, 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 glycosamin oglycan (GAG) side chains in CAA in brains of patients with AD and HCHWA-D. Hereto, specific well-characterized antibodies directed against the core p rotein of these HSPGs and against the GAG side chains were used for immunos taining. 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. Coloca lization of agrin with vascular A beta was clearly observed in CAA in HCHWA -D brains, but only in a minority of the AD cases. Conversely, syndecan-2 w as frequently associated with vascular A beta in AD, but did not colocalize with vascular A beta deposits in HCHWA-D. The three different syndecans, a grin, glypican-1 and HS GAG, but not perlecan, were associated with the maj ority 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 pathog enesis 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 m ay 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 o f HSPG species.