Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis

Elisabet Ihse, Claudio Rapezzi, Giampaolo Merlini, Merrill Benson, Yukio Ando, Ole B. Suhr, Shu Ichi Ikeda, Francesca Lavatelli, Laura Obici, Candida C. Quarta, Ornella Leone, Hirofumi Jono, Mitsuharu Ueda, Massimiliano Lorenzini, Juris Liepnieks, Toshinori Ohshima, Masayoshi Tasaki, Taro Yamashita, Per Westermark

Research output: Contribution to journalArticle

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Abstract

The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one consisting of mainly intact ATTR (type B). The fibril types are correlated to phenotypic differences. Patients with ATTR fragments have a late onset and develop cardiomyopathy, while patients without fragments have an early onset and less myocardial involvement. The present study aimed to determine whether this correlation between fibril type and phenotype is valid for familial ATTR amyloidosis in general. Cardiac or adipose tissues from 63 patients carrying 29 different TTR non-V30M mutations as well as 13 Japanese ATTRV30M patients were examined. Fibril type was determined by western blotting and compared to the patients' age of onset and degree of cardiomyopathy. All ATTR non-V30M patients had a fibril composition with ATTR fragments, except two ATTRY114C patients. No clear conclusions could be drawn about a phenotype to fibril type correlation among ATTR non-V30M patients. In contrast, Japanese ATTRV30M patients showed a similar correlation as previously described for Swedish ATTRV30M patients. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis, and suggests that fibrils composed of only full-length ATTR is an exception found only in a subset of patients.

Original languageEnglish
Pages (from-to)142-150
Number of pages9
JournalAmyloid
Volume20
Issue number3
DOIs
StatePublished - Sep 2013

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Amyloidosis
Amyloid
Familial Amyloidosis
Phenotype
Cardiomyopathies
Mutation
Age of Onset
Adipose Tissue
Western Blotting

Keywords

  • Familial amyloidotic polyneuropathy
  • Fibril composition
  • Transthyretin
  • TTR non-V30M
  • TTRV30M
  • TTRY114C

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis. / Ihse, Elisabet; Rapezzi, Claudio; Merlini, Giampaolo; Benson, Merrill; Ando, Yukio; Suhr, Ole B.; Ikeda, Shu Ichi; Lavatelli, Francesca; Obici, Laura; Quarta, Candida C.; Leone, Ornella; Jono, Hirofumi; Ueda, Mitsuharu; Lorenzini, Massimiliano; Liepnieks, Juris; Ohshima, Toshinori; Tasaki, Masayoshi; Yamashita, Taro; Westermark, Per.

In: Amyloid, Vol. 20, No. 3, 09.2013, p. 142-150.

Research output: Contribution to journalArticle

Ihse, E, Rapezzi, C, Merlini, G, Benson, M, Ando, Y, Suhr, OB, Ikeda, SI, Lavatelli, F, Obici, L, Quarta, CC, Leone, O, Jono, H, Ueda, M, Lorenzini, M, Liepnieks, J, Ohshima, T, Tasaki, M, Yamashita, T & Westermark, P 2013, 'Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis', Amyloid, vol. 20, no. 3, pp. 142-150. https://doi.org/10.3109/13506129.2013.797890
Ihse, Elisabet ; Rapezzi, Claudio ; Merlini, Giampaolo ; Benson, Merrill ; Ando, Yukio ; Suhr, Ole B. ; Ikeda, Shu Ichi ; Lavatelli, Francesca ; Obici, Laura ; Quarta, Candida C. ; Leone, Ornella ; Jono, Hirofumi ; Ueda, Mitsuharu ; Lorenzini, Massimiliano ; Liepnieks, Juris ; Ohshima, Toshinori ; Tasaki, Masayoshi ; Yamashita, Taro ; Westermark, Per. / Amyloid fibrils containing fragmented ATTR may be the standard fibril composition in ATTR amyloidosis. In: Amyloid. 2013 ; Vol. 20, No. 3. pp. 142-150.
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AU - Ando, Yukio

AU - Suhr, Ole B.

AU - Ikeda, Shu Ichi

AU - Lavatelli, Francesca

AU - Obici, Laura

AU - Quarta, Candida C.

AU - Leone, Ornella

AU - Jono, Hirofumi

AU - Ueda, Mitsuharu

AU - Lorenzini, Massimiliano

AU - Liepnieks, Juris

AU - Ohshima, Toshinori

AU - Tasaki, Masayoshi

AU - Yamashita, Taro

AU - Westermark, Per

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N2 - The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one consisting of mainly intact ATTR (type B). The fibril types are correlated to phenotypic differences. Patients with ATTR fragments have a late onset and develop cardiomyopathy, while patients without fragments have an early onset and less myocardial involvement. The present study aimed to determine whether this correlation between fibril type and phenotype is valid for familial ATTR amyloidosis in general. Cardiac or adipose tissues from 63 patients carrying 29 different TTR non-V30M mutations as well as 13 Japanese ATTRV30M patients were examined. Fibril type was determined by western blotting and compared to the patients' age of onset and degree of cardiomyopathy. All ATTR non-V30M patients had a fibril composition with ATTR fragments, except two ATTRY114C patients. No clear conclusions could be drawn about a phenotype to fibril type correlation among ATTR non-V30M patients. In contrast, Japanese ATTRV30M patients showed a similar correlation as previously described for Swedish ATTRV30M patients. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis, and suggests that fibrils composed of only full-length ATTR is an exception found only in a subset of patients.

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