These proteins normally circulate in the blood but may undergo conformational changes that cause them to auto-aggregate along their beta-pleated sheets to become insoluble and form fibril deposits in and outside of the circulation. These deposits disrupt tissue architecture and, in the case of light chains, directly injure cells, thereby causing potentially cataclysmic organ failures. There are 31 types of circulating proteins that can become misfolded and lead to distinctly different types of amyloidosis; among these, myeloma proteins, particularly free light chains, are the predominant cause of the disease. Increases in the levels of free κ or λ light chains are a common feature of plasma cell dyscrasias. These increases occur in: 40% of IgM MGUS, IgM SMM, and Waldenstroms macroglbulonemia cases; 60% to 70% of non-secretory multiple myelom cases;  90% to 95% of intact immunoglobulin multiple myeloma cases; and, by definition, 100% of light chain multiple myeloma cases. There are two different types of plasma cell dyscrasia-associated amyloidosis syndromes: amyloid light chain amyloidosis (AL amyloidosis) in which amyloid deposits consist of free light chains and amyloid heavy chain amyloidosis (AH amyloidosis) in which amyloid deposits contain only free heavy chains. The deposits in a third type, AHL amyloidosis, consists of both free light chains and free heavy chains. AHL amyloidosis is here, as in some recent reports, grouped with AH amyloidosis. AL Amyloidosis
AL amyloidosis can occur at any stage in the plasma cell dyscrasia spectrum.
However, more sensitive methods of detecting urinary and serum light chain myeloma proteins using enzyme-linked immunosorbent assays indicate that >60% of cases initially diagnosed as non-secretory multiple myeloma had abnormal levels of either a clonal κ or λ light chain in their urine or serum and therefore were better diagnosed as having light chain multiple myeloma. Based on the latter definition, non-secretory multiple myeloma represents ~1% of all multiple myeloma cases with formerly diagnosed non-secretory myelomas considered to be cases primarily of light chain multiple myeloma but on occasion "false non-secretors", i.e. cases in which there is evidence of myeloma protein secretion such as renal myeloma protein deposits.A Mayo Clinic study of 124 patients initially diagnosed as having non-secretory multiple myeloma were later found to be composed of 65% free light chain secretors and 35% true non-secretors. As a group, these patients response to therapy, time to disease recurrence, and overall survival were similar to typical myeloma patients. However, in a subset of patients diagnosed after 2001 and therefore treated with more effective therapy that included autologous stem-cell transplantation, prognosis was significantly better in non-secretory multiple myeloma patients (median survival 8.3 years) compared to typical myeloma patients (median survival 5.4 years). In addition, non-secretory patients exhibited a better prognosis than light chain-secretory patients.