Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy

J Neurol Sci. 2009 Dec 15;287(1-2):178-84. doi: 10.1016/j.jns.2009.07.028. Epub 2009 Aug 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / metabolism
  • Adrenal Glands / pathology
  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Amino Acid Sequence / genetics
  • Amino Acid Substitution / genetics
  • Amyloid / genetics*
  • Amyloid / metabolism
  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / pathology*
  • Coloring Agents
  • Congo Red
  • DNA Mutational Analysis
  • Female
  • Genetic Markers / genetics
  • Genetic Testing
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Methionine / genetics
  • Methionine / metabolism
  • Middle Aged
  • Myocardium / metabolism
  • Myocardium / pathology
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology*
  • Peripheral Nerves / physiopathology
  • Prealbumin / chemistry
  • Prealbumin / genetics*
  • Staining and Labeling / methods
  • Valine / genetics
  • Valine / metabolism
  • Viscera / metabolism
  • Viscera / pathology*
  • Viscera / physiopathology
  • Young Adult


  • Amyloid
  • Coloring Agents
  • Genetic Markers
  • Prealbumin
  • Congo Red
  • Methionine
  • Valine