title: Deposition and passage of transthyretin through the blood-nerve barrier in recipients of familial amyloid polyneuropathy livers.
abstract: Familial amyloid polyneuropathy (FAP) is characterized by deposition of mutated transthyretin (TTR) in the peripheral nervous system. Prior to amyloid fibrils, nonfibrillar TTR aggregates are deposited inducing oxidative stress with increased nitration (3-NT). As the major source of TTR is the liver, liver transplantation (LT) is used to halt FAP. Given the shortage of liver donors, domino LT (DLT) using FAP livers is performed. The correlation between TTR deposition in the skin and nerve was tested in biopsies from normal individuals, asymptomatic carriers (FAP 0) and FAP patients; in FAP 0, nonfibrillar TTR was observed both in the skin and nerve in the same individuals; in patients, amyloid was detected in both tissues. The occurrence of amyloidosis in recipients of FAP livers was evaluated 1-7 years after DLT: TTR deposition occurred in the skin 3 years after transplantation either as amyloid or aggregates; in one of the recipients, fibrillar TTR was present in the epineurium 6 years after DLT. Deposits were scarce and 3-NT immunostaining was irrelevant. Nerve biopsies from DLT recipients had no FAP-related neuropathy. Our findings suggest that TTR amyloid formation occurs faster than predicted and that TTR of liver origin can cross the blood-nerve barrier. Recipients of FAP livers should be under surveillance for TTR deposition and tissue damage.
authors.affiliation: Molecular Neurobiology, Institute for Cellular and Molecular Biology, Rua Campo Alegre 823, 4150-180 Porto, Portugal.
authors.forename: Mónica M
authors.initials: MM
authors.lastname: Sousa
authors.forename: José
authors.initials: J
authors.lastname: Ferrão
authors.forename: Rui
authors.initials: R
authors.lastname: Fernandes
authors.forename: António
authors.initials: A
authors.lastname: Guimarães
authors.forename: José B
authors.initials: JB
authors.lastname: Geraldes
authors.forename: Rui
authors.initials: R
authors.lastname: Perdigoto
authors.forename: Luís
authors.initials: L
authors.lastname: Tomé
authors.forename: Oscar
authors.initials: O
authors.lastname: Mota
authors.forename: Luís
authors.initials: L
authors.lastname: Negrão
authors.forename: Alexandre Linhares
authors.initials: AL
authors.lastname: Furtado
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Saraiva
mesh_terms: D000328:Adult; D028227:Amyloid Neuropathies, Familial / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000686:Amyloidosis / Q000209:etiology; D001706:Biopsy; D005260:Female; D006801:Humans; D008099:Liver / Q000294:innervation / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism*; D012867:Skin / Q000473:pathology
chemical_list: D011228:Prealbumin