THE PUTATIVE ROLE OF ALPHA-1-ANTITRYPSIN IN THE DISAGGREGATION OF AMYLOID-LAMBDA FIBRILS

Background and objectives. Interactions between hydrophobic compounds like cholesterol and lithocholic acid and alpha-1-antitrypsin (alpha-1 -AT) have previously been described. We studied the putative interacti on between alpha-1-AT and the insoluble, hydrophobic, beta-pleated she et, light-chain-derived fibrils that predominate the tissue deposits i n primary immunocytic (AL) related amyloidosis. Subjects and methods. Amyloid fibrils were isolated from two cases with lambda and two cases with kappa AL amyloidosis. Results. The lambda fibrils could be compl etely disaggregated (as shown by light and electron microscopy and Con go red uptake) by alpha-1-AT added in the molar ratio 1:5, whereas fib rils with predominantly kappa chains remained unaffected. The lambda-c hain interaction was accompanied by characteristic changes of the phys icochemical and biological properties of alpha-1-AT from a native, str essed conformation to a relaxed form. Conclusions. Disaggregation of l ambda AL amyloid fibrils can be achieved by addition of alpha-1-AT. Th e findings may have therapeutic implications in primary amyloidosis.