title: Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy.
abstract: Late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) cases unrelated to endemic foci in Japan show different clinicopathological features from the conventional early-onset cases in endemic foci. We compared the characteristics of amyloid deposits in early-onset FAP ATTR Val30Met cases in endemic foci and late-onset cases in non-endemic areas. Amyloid deposits in three early-onset cases from endemic foci and five late-onset cases from non-endemic areas were systematically examined post-mortem. Amyloid deposits in early-onset cases were highly congophilic and showed strong apple-green birefringence with Congo red staining and had long, parallel fibrils in most organs. On the other hand, those in late-onset cases were generally weakly congophilic and showed faint apple-green birefringence with Congo red staining and had short, haphazard fibrils. In the renal glomus and adrenal gland of early-onset cases, the characteristics of amyloid deposits were similar to those observed in late-onset cases. Analysis of cardiac amyloid using surface enhanced desorption/ionization time-of-flight mass spectrometry indicated that most transthyretin (TTR) was variant in early-onset cases, while more than half was composed of wild-type TTR in late-onset cases. Although characteristics of amyloid deposits may differ among individual organs of respective cases, especially in early-onset cases, the pattern was distinct between early- and late-onset cases. Amyloid deposition in late-onset cases may be similar to that observed in senile systemic amyloidosis with wild-type TTR deposition, suggesting that aging may play an important role in these cases.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Koike
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawagashira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iijima
authors.forename: Junko
authors.initials: J
authors.lastname: Fujitake
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Hayashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Mukai
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Naoki
authors.initials: N
authors.lastname: Hattori
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology*; D004396:Coloring Agents; D003224:Congo Red; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008715:Methionine / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics*; D013194:Staining and Labeling / Q000379:methods; D014633:Valine / Q000235:genetics / Q000378:metabolism; D014781:Viscera / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000682:Amyloid; D004396:Coloring Agents; D005819:Genetic Markers; D011228:Prealbumin; D003224:Congo Red; D008715:Methionine; D014633:Valine