A NEW SIMPLE AND RAPID SCREENING METHOD FOR VARIANT TRANSTHYRETIN-RELATED AMYLOIDOSIS

To screen for transthyretin (TTR) related amyloidosis rapidly and reli ably, we have developed a new method using a centrifugal concentrator device and electrospray ionization mass spectrometry (ESI-MS). Only 50 mu l of serum is needed for the analysis. After preparation of the sa mples with anti-TTR antibody they were passed through a 1000 kDa cut o ff centrifugal concentrator which retained the antibody. By analyzing the obtained filtrate with ESI-MS, variant forms of TTR was detected T TR (Met30), with a molecular weight 32.0 Da higher than the normal for m of TTR, was found in all FAP patients examined. In 3 liver transplan ted FAP patients. the abnormal peaks had disappeared. In conclusion, T he TTR Met30 mutation was easily detected in serum samples by electros pray ionization mass spectrometry after centrifugal concentration. The proposed method is simple to perform, as no HPLC is required, and off ers a possibility to screen populations for TTR related amyloidosis. ( C) 1996 Academic Press, Inc.