ULTRASTRUCTURAL ORGANIZATION OF HEMODIALYSIS-ASSOCIATED BETA(2)-MICROGLOBULIN AMYLOID FIBRILS

Fibrils of hemodialysis-associated beta(2)-microglobulin amyloid were examined by high resolution electron microscopy and immunohistochemica l labeling. The amyloid containing tissues obtained through autopsy we re prepared for thin section observations. In contrast to other forms of amyloid, the most conspicuous feature of these fibrils were their c urved conformations. The fibril core showed ultrastructural and immuno histochemical features in common with the core of connective tissue mi crofibrils and of previously observed fibrils of experimental murine A A amyloidosis and familial amyloid polyneuropathy (FAP). The core was wrapped in a layer of 3 nm wide ribbon-like ''double tracked'' structu res identified as chondroitin sulfate proteoglycan (CSPG) with immunog old labeling as well as from the results of previous in vitro experime nts. Finally, the outer surface of the fibril was associated with a lo ose assembly of 1 nm wide filaments immunohistochemically identified a s beta(2)-microglobulin. This is similar to the manner in which AA pro tein and transthyretin filaments are associated with their respective fibrils. The results of this study provide an additional example for t he concept that amyloid fibrils in general are microfibril-like struct ures externally associated with amyloid protein filaments. An unusual feature of the fibrils of hemodialysis-associated amyloid, however, is the presence of a peripheral layer composed of CSPG rather than of he paran sulfate proteoglycan (HSPG) as in the case of the other two amyl oids above. These chondroitin sulfate chains in the outer CSPG layer m ay be less effective in providing rigidity to the fibril core, thus al lowing for the curved conformations of beta(2)-microglobulin amyloid f ibrils.