title: Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation.
abstract: OBJECTIVE
  To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP).
  
  
  METHODS
  We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients.
  
  
  RESULTS
  Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan.
  
  
  CONCLUSIONS
  FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Kawahara
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Okazaki
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohya
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ihse
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.affiliation: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Asonuma
authors.affiliation: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000682:Amyloid / Q000032:analysis; D028227:Amyloid Neuropathies, Familial / Q000473:pathology*; D004396:Coloring Agents; D003224:Congo Red; D005260:Female; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry; D011228:Prealbumin / Q000032:analysis; D013116:Spinal Cord / Q000737:chemistry; D013997:Time Factors; D014059:Tongue / Q000737:chemistry
chemical_list: D000682:Amyloid; D004396:Coloring Agents; D011228:Prealbumin; D003224:Congo Red
keywords: Amyloid; Genetics; Pathology