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

Jack Horssen, Irene Otte-Höller, Guido David, Marion L. Maat-Schieman, Lambert P. Heuvel, Pieter Wesseling, Robert M. Waal, Marcel M. Verbeek

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

88 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)604-614
Aantal pagina's11
TijdschriftActa Neuropathologica
Volume102
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 2001
Extern gepubliceerdJa

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