Polysaccharides in Alzheimer's disease and inflammation-associated amyloidosis
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
Amyloidosis is a term for diseases that share a common feature: the extracellular deposition of amyloid fibrils, that consist of a single protein prone to aggregate. Polysaccharides (glycos-aminoglycans), especially heparan sulfate, are significant components of all types of amyloid deposits. Arising from numerous modifications during biosynthesis, heparan sulfate is characterized by extensive structural variability that affects interactions with various proteins and thus influences important biological functions.
The aim of this study was to characterize heparan sulfate from Alzheimer lesions in cerebral cortex and from amyloidotic liver and spleen following inflammation-associated amyloidosis. We wanted to determine whether Alzheimer's disease is associated with structural changes in heparan sulfate that could possibly affect the interaction with the amyloid β-peptide, the main constituent of amyloid deposits in brain. Amyloid laden liver and spleen showed a substantial increase in heparan sulfate, while no such increase was noted in Alzheimer diseased brains compared to control material. On the other hand keratan sulfate, another glycosaminoglycan, identified biochemically and by immunohistochemical analysis in Alzheimer diseased cerebral cortex, was reduced to less than half of the amount in control tissue.
Cerebral heparan sulfate differed in composition from that of other organs. This distinctive composition appeared unchanged in Alzheimer's disease. Binding of human cerebral heparan sulfate to synthetic amyloid β-peptide was demonstrated and oligosaccharide domains interacting with non-fibrillar and fibrillar amyloid β-peptide were identified and partially characterized. This interaction is part of the complex amyloid formation process and provides a potential target for therapy; agents inhibiting these interactions might preclude amyloid deposition.
Contrary to the cerebral polysaccharide, heparan sulfate from amyloidotic liver and spleen showed a distinct, presumably amyloid-specific, composition that differed from those of the corresponding control materials.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1998. , 52 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 758
Medical sciences, Alzheimer's disease, amyloid, heparan sulfate, keratan sulfate
MEDICIN OCH VÅRD
Medical and Health Sciences
Research subject Medical Pharmacology
IdentifiersURN: urn:nbn:se:uu:diva-176ISBN: 91-554-4202-1OAI: oai:DiVA.org:uu-176DiVA: diva2:161336
1998-06-05, Auditorium Minus, Gustavianum, Uppsala, Uppsala, 13:15