Analysis of transthyretin amyloid fibrils from vitreous samples in familial amyloidotic polyneuropathy (Val Met)

Abstract

The aim of the present study was to analyze the forms of wild type and mutated monomeric transthyretin (Val3 et) in the amyloid fibrils of patients with familial amyloidotic polyneuropathy by electrospray ionization mass spectrometry (ESI-MS). The solubility of amyloid fibrils from the vitrectomized samples was examined to determine the appropriate solution for ESI-MS. ESI-MS analysis revealed that heterozy-gotic Val3 et amyloid fibrils contained 14.6 ± 7.5 % normal TTR. In all samples, 3 different types of variant ATTR could be identified: Full length ATTR, and-57, and-157 (or 156) Da from ATTR Val3 et were found. The two peaks showing-57, and-157 (or 156) Da from ATTR Val3 et corresponded to the-Gly, and-Gly-Pro sequences of ATTR Val3 et from the N-terminal. The results illustrate the heterogeneity of ATTR amyloid deposits and this method may be very useful for analyzing amyloid fibrils in ATTR related amyloidosis.