ABSTRACT
Key questions in transthyretin (TTR) amyloidosis include pathways of fibril formation and consequences of TTR deposition. Molecular studies of intermediate species and detection of these intermediates “in vivo” are pivotal to answer the questions and for prospective therapeutical approaches. This chapter summarizes advances in the intermediates of TTR fibrils and tissue changes associated with TTR deposition. Tissue changes associated with TTR deposition have been investigated at the RNA and protein levels in tissues from asymptomatic carriers of TTRV30M and from FAP patients. Microarray analyses revealed changes in a number of different genes. Trends in TTR amyloidosis at the molecular and cellular levels encompass the interplay between inflammation, oxidative stress, matrix remodelling which can be either a consequence of toxicity from intermediate species/amyloid, or be players in TTR deposition.
