Impact of age and amyloidosis on thiol conjugation of transthyretin in hereditary transthyretin amyloidosis

Variant forms and post-translational modifications of transthyretin (TTR) c an be identified by electrospray ionisation mass spectrometry (ESI-MS). The aim of the present study was to investigate thiol conjugation of transthyr etin and it's relation to age and symptomatic amyloid disease in different populations of variant TTR carriers. Plasma samples from 70 individuals from Denmark, Argentina, Sweden and Japa n, with 2 different TTR mutations were analysed. The percentage cysteine (C ys) conjugated wild and variant TTR were calculated from the corresponding peaks of the spectra, and multiple regression analysis was employed to disc lose relationships between age, symptomatic amyloid disease and origin. Age, origin and presence of symptomatic disease, were found to be independe nt factors related to transthyretin conjugation. A higher percentage of con jugated to unconjugated TTR was disclosed in symptomatic, but not in asympt omatic carriers. In summary: Thiol conjugation of TTR is dependent on age a nd presence of symptomatic amyloid disease. Furthermore, it varies between different populations. Variant TTR is more susceptible to thiol conjugation than the wild type. Post-translational factors may be related to amyloid f ormation and/or toxicity.