Journal
ACTA NEUROPATHOLOGICA
Volume 119, Issue 2, Pages 211-220Publisher
SPRINGER
DOI: 10.1007/s00401-009-0577-1
Keywords
Alzheimer's disease; Amyloid-beta plaques; Heparan sulfate; Sulfation
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Funding
- Internationale Stichting Alzheimer Onderzoek (ISAO) [07510]
- Netherlands Organisation for Scientific Research (NWO/ZonMW, Vidi program) [917.46.331]
- Hersenstichting Nederland [14F06.18]
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Alzheimer's disease (AD) is characterized by pathological lesions such as amyloid-beta (A beta) plaques and cerebral amyloid angiopathy. Both these lesions consist mainly of aggregated A beta protein and this aggregation is affected by macromolecules such as heparan sulfate (HS) proteoglycans. Previous studies demonstrated that HS enhances fibrillogenesis of A beta and that this enhancement is dependent on the degree of sulfation of HS. In addition, it has been reported that these sulfation epitopes do not occur randomly but have a defined tissue distribution. Until now, the distribution of sulfation epitopes of HS has not yet been studied in human brain. We investigated whether a specific HS epitope is associated with A beta plaques by performing immunohistochemistry on occipital neocortical and hippocampal tissue sections from AD patients using five HS epitope-specific phage display antibodies. Antibodies recognizing highly N-sulfated HS demonstrated the highest level of staining in both fibrillar A beta plaques and non-fibrillar A beta plaques, whereas antibodies recognizing HS regions with a lower degree of N-sulfate modifications were only immunoreactive with fibrillar A beta plaques. Thus, our results suggest that a larger variety of HS epitopes is associated with fibrillar A beta plaques, but the HS epitopes associated with non-fibrillar A beta plaques seem to be more restricted, selectively consisting of highly N-sulfated epitopes.
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