Amyloid deposits in transthyretin-derived amyloidosis

Cleaved transthyretin is associated with distinct amyloid morphology

Joakim Bergström, Åsa Gustavsson, Ulf Hellman, Knut Sletten, Charles L. Murphy, Deborah T. Weiss, Alan Solomon, Bert Ove Olofsson, Per Westermark

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

The pathological fibrillar deposits found in the heart and other organs of patients with senile systemic amyloidosis (SSA) and Swedish familial amyloidotic polyneuropathy (FAP) contain wild-type (wt) and a mutant form of transthyretin (TTR), respectively. Previously, it was reported that these two forms of amyloid have different molecular features and it was thus postulated that the mechanism responsible for TTR fibrillogenesis in SSA and FAP may differ. To document further the nature of the amyloid in these entities, detailed morphological, histochemical, immunological, and structural analyses of specimens obtained from 14 individuals with SSA and 11 Swedish FAP patients have been performed. Two distinct patterns of amyloid deposition (designated A and B) were evident. In pattern A, found in all SSA and five of 11 FAP cases, the amyloid had a homogeneous but patchy distribution within the sub-endocardium, sub-epicardium, and myocardium; exhibited weak congophilia and green birefringence; and was composed of tightly packed, short, unorientated fibrils. This material contained mainly ∼79-residue C-terminal fragments of the amyloidogenic precursor protein. In pattern B, seen in the six other FAP patients, the amyloid appeared as thin streaks throughout the cardiac tissue; often surrounded individual muscle cells; was strongly congophilic and birefringent; had long fibrils arranged in parallel bundles, often penetrating into myocytes; and was composed of virtually intact TTR molecules. These findings provide substantive evidence for the morphological and structural heterogeneity of TTR fibrils and suggest that the two types of deposition may reflect fundamental differences in the pathogenesis of the TTR-associated amyloidoses.

Original languageEnglish (US)
Pages (from-to)224-232
Number of pages9
JournalJournal of Pathology
Volume206
Issue number2
DOIs
StatePublished - Jun 1 2005

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Prealbumin
Polyneuropathies
Amyloid Plaques
Amyloid
Amyloidosis
Muscle Cells
Birefringence
Amyloidogenic Proteins
Endocardium
Pericardium
Myocardium
Amyloidosis, Hereditary, Transthyretin-Related

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Bergström, J., Gustavsson, Å., Hellman, U., Sletten, K., Murphy, C. L., Weiss, D. T., ... Westermark, P. (2005). Amyloid deposits in transthyretin-derived amyloidosis: Cleaved transthyretin is associated with distinct amyloid morphology. Journal of Pathology, 206(2), 224-232. https://doi.org/10.1002/path.1759

Amyloid deposits in transthyretin-derived amyloidosis : Cleaved transthyretin is associated with distinct amyloid morphology. / Bergström, Joakim; Gustavsson, Åsa; Hellman, Ulf; Sletten, Knut; Murphy, Charles L.; Weiss, Deborah T.; Solomon, Alan; Olofsson, Bert Ove; Westermark, Per.

In: Journal of Pathology, Vol. 206, No. 2, 01.06.2005, p. 224-232.

Research output: Contribution to journalArticle

Bergström, J, Gustavsson, Å, Hellman, U, Sletten, K, Murphy, CL, Weiss, DT, Solomon, A, Olofsson, BO & Westermark, P 2005, 'Amyloid deposits in transthyretin-derived amyloidosis: Cleaved transthyretin is associated with distinct amyloid morphology', Journal of Pathology, vol. 206, no. 2, pp. 224-232. https://doi.org/10.1002/path.1759
Bergström, Joakim ; Gustavsson, Åsa ; Hellman, Ulf ; Sletten, Knut ; Murphy, Charles L. ; Weiss, Deborah T. ; Solomon, Alan ; Olofsson, Bert Ove ; Westermark, Per. / Amyloid deposits in transthyretin-derived amyloidosis : Cleaved transthyretin is associated with distinct amyloid morphology. In: Journal of Pathology. 2005 ; Vol. 206, No. 2. pp. 224-232.
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