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Highly sulfated glycosaminoglycans (GAG) or proteoglycans (PG), especially heparan sulfate (HS) and heparan sulfate proteoglycan (HSPG), are considered to be intimately associated with amyloid deposits in different types of amyloidosis. Based on this relationship an important role for HS has been suggested in amyloidogenesis. The present immunohistological and ultrastructural study shows that in bovine renal AA-amyloidosis, sulfated GAG/PG was not restricted to amyloid deposits proper and that areas without GAP/PG were also present within the amyloid. Both glomerular and papillary amyloid contained HS (PG), and the latter also contained chondroitin sulfate (CS) and dermatan sulfate (DS), suggesting a correlation between the location of the amyloid and the type of GAG/PG deposited. Amyloid P component (AP) had a distribution similar to that of HSPG, confirming their affinity-based relationship. The GAG types found ultrastructurally in amyloid fibril preparations of glomerular and papillary amyloid isolated from the same kidney, reflected the immunohistological findings. HS was shown to be the predominant GAG in all papillary amyloid fibril extracts. Taking into account the chemico-physical properties of HS, it cannot be excluded that this predominance is introduced by the purification procedure. These results suggest that the association of GAG/PG and amyloid is not necessarily mutually obligatory and that the proposed importance of GAG in amyloidogenesis is disputable.

The evidence that glycosaminoglycans (GAGs) are specifically associated with amyloid, is strong. In the present study we looked for GAGs in water extracts of amyloid fibrils from kidney and spleen laden with AA amyloid secondary to ankylosing spondylitis. Significant amounts of high molecular weight GAGs were isolated from the fibril preparations of both organs using ion-exchange chromatography and gel filtration procedures. The polysaccharides present in purified human renal and splenic amyloid fibril material were characterized as follows: a) Sulphated GAGs of high molecular weight were found in both renal and splenic amyloid fibril extracts, but not in extracts from corresponding normal tissues. b) All of the renal amyloid-associated high molecular weight GAGs were chondroitin sulphate/dermatan sulphate, whereas splenic amyloid-associated high molecular weight GAGs had a chondroitin sulphate/dermatan sulphate:heparan sulphate ratio of approximately 2:1. c) The findings gave no evidence that GAGs coisolated with AA amyloid fibrils were parts of intact proteoglycan molecules with several GAG chains.

Significant amounts of glycosaminoglycans (GAGs) were found in amyloid fibril preparations. Using two-dimensional electrophoresis to fractionate GAG mixtures, we quantified and identified for the first time the GAGs of the fibrils from carpal synovium of patients with amyloid associated with chronic hemodialysis. The total GAG content was small, but the GAG distribution (high relative content of chondroitin sulfate and hyaluronic acid and lack of the other GAGs) was unique, unlike that for the other amyloid fibril preparations. The amyloid-rich heart, liver, and spleen tissues, as well as the fibrils isolated from these tissues of patients with systemic forms (primary amyloid and secondary amyloid) of amyloid disease, were also analyzed for GAGs. Fibrils from heart tissue of a patient with primary amyloidosis, now examined for the first time, contained four major GAGs (chondroitin sulfate, dermatan sulfate, hyaluronic acid, and heparan sulfate).

Previous studies have strongly suggested an association between glycosaminoglycans and tissue deposits of amyloid. The present study was aimed at studying this association in purified preparations of hepatic amyloid fibrils obtained from human AA type secondary amyloidosis. Glycosaminoglycans were isolated by gradient ion exchange chromatography of purified amyloid fibrils treated with pronase. Degradation with specific enzymes identified the glycosaminoglycans as chondroitin sulphate, dermatan sulphate, and heparin/heparan sulphate. The total amount of glycosaminoglycans specifically coisolated with the amyloid fibrils was 15 micrograms/mg fibril weight. The presence of glycosaminoglycans in amyloid may play a part in the incorporation of structurally diverse protein precursors into amyloid fibrils of identical ultrastructure.