title: Effect of age and sex differences on wild-type transthyretin amyloid formation in familial amyloidotic polyneuropathy: a proteomic approach.
abstract: BACKGROUND
  Age and sex differences are closely related to the onset of senile systemic amyloidosis (SSA) caused by wild-type (WT) transthyretin (TTR). However, the effects of these differences on the amyloid formation mechanism in familial amyloid polyneuropathy (FAP) caused by variant TTR, have remained unclear. To elucidate age and sex differences in FAP, we investigated biochemical characteristics of amyloid deposits in different tissue sites of FAP by proteomic analysis.
  
  
  METHODS
  We used shotgun liquid chromatography/tandem mass spectrometry to analyze the proportions of variant and WT TTR in amyloid deposits in different tissues, such as cardiac, kidney, peripheral nerves, and gastrointestinal tissues, from 23 autopsied FAP cases.
  
  
  CONCLUSIONS
  The analysis revealed a highly significant correlation between the proportion of WT TTR and age at autopsy in cardiac tissues, whereas the analysis indicated no correlation in kidney, peripheral nerves, and gastrointestinal tissues. In addition, we demonstrated age-related significantly increased WT TTR deposits, but not variant TTR deposits, in cardiac tissues of male patients. Taken together, these data suggest that both age and sex differences affect cardiac amyloid formation, mainly derived from WT TTR, in FAP.
authors.affiliation: Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan; Department of Immunology and Hematology, Division of Informative Clinical Science, Graduate School of Medical Sciences, Kumamoto University, 4-24-1 kuhonji, Kumamoto 862-0976, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Haruki
authors.initials: H
authors.lastname: Koike
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Genki
authors.initials: G
authors.lastname: Suenaga
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oshima
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000367:Age Factors; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D011228:Prealbumin
keywords: Aging; Amyloidosis; Familial amyloidotic polyneuropathy; Proteome; Sex differences; Transthyretin