Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosis
(English)Manuscript (preprint) (Other academic)
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 composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement.
The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy.
Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits.
This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.
amyloid, transthyretin, familial amyloidotic polyneuropathy, non-TTRV30M, TTRV30M, cardiomyopathy, fibril composition
Cell and Molecular Biology Other Basic Medicine Clinical Laboratory Medicine Biochemistry and Molecular Biology
Research subject Biochemistry; Biology with specialization in Molecular Biology; Biomedical Laboratory Science; Experimental Pathology; Medical Biochemistry; Molecular Biology; Pathology
IdentifiersURN: urn:nbn:se:uu:diva-160979OAI: oai:DiVA.org:uu-160979DiVA: diva2:459638