One mutation, two distinct disease variants: unravelling the impact of transthyretin amyloid fibril composition

Abstract

Abstract. Suhr OB, Lundgren E, Westermark P (Ume a University,

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis

“…Amyloid fibril analysis also showed a close association between LV myocardial thickness and the type A ATTR fibrils. In Swedish hereditary ATTR V30M amyloidosis, there are two distinct fibril types [13,14,16,17]. Type A fibrils are composed mainly of N-terminally truncated TTR molecules starting at positions 46, 49 and 52 while type B fibrils consist of full-length TTR molecules.…”

Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

“…Extraction of amyloid fibrils deposited in the hearts of patients suffering from ATTR amyloidosis revealed structural variations and thus polymorphism of the TTR‐derived amyloid fibrils in these patients . Moreover, there is evidence that TTR can undergo different proteolytic processing in different patients . Fibril type A, the predominant fibril type, occurs in one set of patients and is composed of a mixture of full‐length TTR 1‐127 and TTR C‐terminal sequence approximately residues 50–127.…”

Clinicopathological spectrum and recent advances in the treatment of hereditary transthyretin amyloidosis

“…25,26 Biochemical analysis suggests that amyloid fibrils from the early-onset Val30Met cases are mainly composed of full-length TTR, whereas a large amount of C-terminal fragments of TTR, starting at positions of around amino acid 50, are present in the amyloid fibrils from late-onset Val30Met cases. 28,29 Short amyloid fibrils with abundant truncated TTR, similar to those observed in the late-onset Val30Met cases, have also been reported in most non-Val30Met mutation patients. 27,30 Additionally, this latter type of amyloid fibrils is also seen in patients with wild-type ATTR amyloidosis (also known as senile systemic amyloidosis).…”

“…The length of amyloid fibrils is generally long and thick in the former case, and short and thin in the latter case . Biochemical analysis suggests that amyloid fibrils from the early‐onset Val30Met cases are mainly composed of full‐length TTR, whereas a large amount of C‐terminal fragments of TTR, starting at positions of around amino acid 50, are present in the amyloid fibrils from late‐onset Val30Met cases . Short amyloid fibrils with abundant truncated TTR, similar to those observed in the late‐onset Val30Met cases, have also been reported in most non‐Val30Met mutation patients .…”