Objective: To biochemically characterize peripheral nerve amyloid in subjects with transthyretin (TTR) amyloidosis and assess effect of orthotopic liver transplantation (OLT) on progression of neuropathy.
Methods: Amyloid fibrils were isolated from peripheral nerve tissues of 6 patients with TTR amyloidosis who were heterozygous for an amyloid-associated TTR mutation. Ratio of variant to wild-type TTR in the fibrils was determined by amino acid sequencing of tryptic peptides containing either the variant amino acid residue or the corresponding normal amino acid.
Results: Amyloid fibrils from 3 subjects who died without having received a liver transplant were composed of 60%-65% variant TTR and 35%-40% wild-type. Amyloid fibrils from a subject who died 5 years after liver transplantation contained 25% variant and 75% wild-type TTR.
Conclusion: Ratios of variant to wild-type TTR in amyloid patients heterozygous for an amyloid-associated TTR mutation are similar to published ratios for amyloid fibrils in cardiac tissue. Survival after liver transplantation for TTR amyloidosis may be associated with progression of neuropathy due to continued deposition of amyloid derived from wild-type TTR.