Direct evidence for circulating apoSAA as the precursor of tissue AA amyloid deposits

A precursor product study was carried out using tritiated, undenatured murine high-density lipoprotein (HDL)-apoSAA, to assess whether circulating HDL-apoSAA is the precursor of tissue AA amyloid deposits. The quantity of label accumulating in AA over a 24-h period was determined per unit weight of spleen. In addition a mathematical assessment of the quantity of label that should have accumulated in splenic AA within 24 h was made, based on the half-life of circulating apoSAA, the rate of change of the specific activity of circulating apoSAA, and rate of deposition of splenic AA. The observed result was approximately 47% of the theoretically predicted value. The latter did not include extraction efficiencies of AA peptide from spleen nor losses which might have occurred during column fractionation of splenic extracts. The observed and predicted results are therefore in remarkably good agreement and indicate that circulating apoSAA is the major source of protein for splenic AA amyloid deposition.