Authors: Bergström, Joakim¹; Gustavsson, Åsa²; Hellman, Ulf³; Sletten, Knut⁴; Murphy, Charles L⁵; Weiss, Deborah T⁵; Solomon, Alan⁵; Olofsson, Bert-Ove⁶; Westermark, Per¹

Source: The Journal of Pathology, Volume 206, Number 2, June 2005 , pp. 224-232(9)

Publisher: John Wiley & Sons, Ltd.

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. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: amyloidosis; transthyretin; familial amyloid polyneuropathy; senile systemic amyloidosis

Document Type: Research article

DOI: http://dx.doi.org/10.1002/path.1759

Affiliations: 1: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden 2: University of Skövde, Skövde, Sweden 3: Ludwig Institute for Cancer Research, Uppsala, Sweden 4: Department of Biochemistry/Biotechnology Centre of Oslo, University of Oslo, Norway 5: Human Immunology and Cancer Program, University of Tennessee Graduate School of Medicine, Knoxville, TN 37920, USA 6: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

Publication date: 2005-06-01

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• By this author: Bergström, Joakim ;  Gustavsson, Åsa ;  Hellman, Ulf ;  Sletten, Knut ;  Murphy, Charles L ;  Weiss, Deborah T ;  Solomon, Alan ;  Olofsson, Bert-Ove ;  Westermark, Per

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