276 CIRCULATING FORMS OF PLASMA TRANSTHYRETIN IN PATIENTS WITH WILD-TYPE TRANSTHYRETIN AMYLOIDOSIS AND EFFECTS OF TREATMENT WITH TAFAMIDIS

Abstract Introduction Transthyretin (TTR) is a homotetrameric 55-KDa plasma protein that transports thyroxin and retinol complexed to retinol-binding (RBP). TTR misfolding aggregation can lead the extracellular deposition of amyloid (ATTR) representing one most frequent forms amyloidosis in elderly. Aim this study develop native electrophoretic method characterize circulating samples ATTR patients before during treatment with tafamidis, stabilizer. Methods Plasma from (n=6), collected (T0) tafamidis treatment, healthy controls (n=6) were obtained Fondazione Toscana G. Monasterio (Pisa, Italy). separated on 4–20% Tris-Gly polyacrylamide gel. Western blot analysis was performed anti-TTR (DAKO) or anti-RBP (Siemens Healthineer) antibodies. Proteins detected by Clarity ECL substrate (BioRad). Results Circulating qualitatively similar between ATTRwt at T0 controls. In both groups, represented were: dimers trimers (∼37-50 kDa), tetramers RBP 1:1 ratio (∼80 kDa,) 1:2 (∼100 high molecular weight (MW) aggregates (>150 kDa). Neither monomers nor visible. detectable association some higher MW fractions (∼150 kDa, >250 Following all displayed progressive increase intensity band corresponding TTR-RBP complexes, agreement drug stabilizing action tetramers. Interestingly trimers, T0, progressively lost treatment. Conclusions The allowed us detect several fractions. Data suggest pattern control: tetramer exists only equilibrium low forms. Furthermore, appreciate effect RBP. expand our knowledge mechanisms triggering its destabilization even when not mutated.