Agrin is a major heparan sulfate proteoglycan accumulating in Alzheimer's disease brain
| Autor: | Jacob van den Born, Irene Otte-Höller, Lambert P. van den Heuvel, Marcel M. Verbeek, Guido David, Pieter Wesseling, Robert M.W. de Waal |
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| Přispěvatelé: | Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT) |
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Male
Glypican animal structures Syndecans Ubiquitins/metabolism Hippocampus/metabolism Neocortex tau Proteins Heparitin Sulfate/metabolism Perlecan Hippocampus Pathology and Forensic Medicine chemistry.chemical_compound tau Proteins/metabolism Alzheimer Disease medicine Humans Agrin Senile plaques Ubiquitins Heparan Sulfate Proteoglycans/metabolism Aged Membrane Glycoproteins biology Membrane Glycoproteins/metabolism Neurofibrillary tangle Heparan sulfate medicine.disease Proteoglycans/metabolism Immunohistochemistry Cell biology carbohydrates (lipids) Proteoglycan chemistry nervous system Immunology biology.protein Proteoglycans Alzheimer Disease/metabolism Female Neocortex/metabolism Heparitin Sulfate Alzheimer's disease Heparan Sulfate Proteoglycans Agrin/metabolism Regular Articles |
| Zdroj: | The American Journal of Pathology, 155(6), 2115-2125. ELSEVIER SCIENCE INC |
| ISSN: | 0002-9440 |
| Popis: | Heparan sulfate proteoglycans (HSPGs) have been suggested to play an important role in the formation and persistence of senile plaques and neurofibrillary tangles in dementia of the Alzheimer's type (DAT). We performed a comparative immunohistochemical analysis of the expression of the HSPGs agrin, perlecan, glypican-1, and syndecans 1-3 in the lesions of DAT brain neocortex and hippocampus. Using a panel of specific antibodies directed against the protein backbone of the various HSPG species and against the glycosaminoglycan (GAG) side-chains, we demonstrated the following. The basement membrane-associated HSPG, agrin, is widely expressed in senile plaques, neurofibrillary tangles and cerebral blood vessels, whereas the expression of the other basement membrane-associated HSPG, perlecan, is lacking in senile plaques and neurofibrillary tangles and is restricted to the cerebral vasculature. Glypican and three different syndecans, all cell membrane-associated HSPG species, are also expressed in senile plaques and neurofibrillary tangles, albeit at a lower frequency than agrin. Heparan sulfate GAG side chains are also associated with both senile plaques and neurofibrillary tangles. Our results suggest that glycosaminoglycan side chains of the HSPGs agrin, syndecan, and glypican, but not perlecan, may play an important role in the formation of both senile plaques and neurofibrillary tangles. In addition, we speculate that agrin, because it contains nine protease-inhibiting domains, may protect the protein aggregates in senile plaques and neurofibrillary tangles against extracellular proteolytic degradation, leading to the persistence of these deposits. |
| Databáze: | OpenAIRE |
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