ABSTRACT

The amyloidoses are a collection of disorders arising from protein misfolding

and misassembly into insoluble b-rich sheets. Extracellular deposition of the resulting amyloid fibrils disrupts organ function, producing clinical disease.

Originally identified as carbohydrate by Virchow in 1854 (1), amyloid deposits

consist of linear arrays of subunit proteins complexed with glucosaminoglycans

and serum amyloid P (SAP) that stabilize the b-sheet conformation. Amyloid deposition occurs in systemic and organ-limited or localized forms. More than

20 proteins form amyloid fibrils (2). In systemic amyloidosis, the precursor

proteins forming amyloid fibrils dictate organ involvement and the resulting

clinical syndrome. Consequently, typing the amyloid allows disease classifica-

tion, prediction of disease progression, and basis for therapeutic intervention.