Accumulation of heparan sulfate proteoglycans in cerebellar senile plaques

Abstract

Alzheimer's disease (AD) brains are characterized by the presence of senile plaques (SPs), which primarily consist of amyloid beta protein (Abeta). Besides Abeta, several other proteins with the ability to modulate amyloid fibril formation accumulate in SPs, e.g. heparan sulfate proteoglycans (HSPGs). Cerebellar SPs are predominantly of the diffuse type, whereas fibrillar SPs are rarely observed. Furthermore, because of the spatial separation of non-fibrillar and fibrillar SPs in the cerebellum, this brain region provides a model for the study of the association of Abeta-associated factors with various stages of SP formation. In the present study, we performed an immunohistochemical analysis to investigate the expression of the HSPG species agrin, perlecan, glypican-1 and the syndecans 1-3 as well as glycosaminoglycan side-chains in cerebellar SPs. We demonstrated that agrin and glypican-1 were expressed in both non-fibrillar and fibrillar cerebellar SPs, whereas the syndecans were only associated with fibrillar cerebellar SPs. Perlecan expression was absent in all cerebellar SPs. Since fibrillar and non-fibrillar SPs may develop independently in the cerebellum, it is likely that agrin, glypican-1 as well as heparan sulfate glycosaminoglycans may contribute to the formation of both cerebellar plaque types, whereas syndecan only seems to play a role in the generation of cerebellar fibrillar plaques.