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Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis.

https://arctichealth.org/en/permalink/ahliterature92323
Source
J Pathol. 2008 Oct;216(2):253-61
Publication Type
Article
Date
Oct-2008
Author
Ihse E.
Ybo A.
Suhr Ob
Lindqvist P.
Backman C.
Westermark P.
Author Affiliation
Department of Genetics and Pathology, Uppsala University, Sweden.
Source
J Pathol. 2008 Oct;216(2):253-61
Date
Oct-2008
Language
English
Publication Type
Article
Keywords
Abdominal Fat - chemistry - pathology
Adult
Age of Onset
Amino Acid Substitution
Amyloid - analysis - genetics - ultrastructure
Amyloidosis, Familial - genetics - pathology - ultrasonography
Blotting, Western - methods
Cardiomyopathies - genetics - pathology
Echocardiography
Electrophoresis, Polyacrylamide Gel - methods
Female
Heart Septal Defects, Ventricular - genetics - pathology - ultrasonography
Humans
Male
Methionine - genetics
Middle Aged
Prealbumin - chemistry - genetics - metabolism
Sweden
Valine - genetics
Abstract
Swedish familial systemic amyloidosis with polyneuropathy (FAP) depends on a mutation leading to a methionine-for-valine substitution in transthyretin. The disease appears with different clinical manifestations, including age of onset and involvement of the heart. Liver transplantation is currently the only curative treatment, but progressive cardiomyopathy may occur post-transplant. Two amyloid deposition patterns have previously been described in the heart. In one, the amyloid consists partially of transthyretin fragments and is weakly stainable by Congo red, while in the other, only full-length molecules are found and the fibrils have a strong affinity for Congo red. The present study aimed to see whether these morphological and biochemical variations have clinical implications. Subcutaneous adipose tissue biopsies were taken from 33 patients with Val30Met FAP and examined by microscopy, electrophoresis and western blot. Clinical data included age, sex, duration of disease and echocardiographic determination of the interventricular septum (IVS) thickness. It was found that fibrils composed of only full-length transthyretin were associated with early age of onset (44.8 +/- 12.9 years), no clinical cardiac involvement and a strong affinity for Congo red. In contrast, presence of transthyretin fragments in the amyloid was associated with late age of onset (67.3 +/- 7.0 years), signs of cardiac involvement and weak Congo red staining. For each individual, the same molecular type of amyloid was found in different organs. This is the first report showing that variations in clinical appearance of familial ATTR amyloidosis are associated with specific structural differences in the amyloid fibrils, and therefore may have a molecular cause. The molecular type of amyloid can be determined from a subcutaneous fat tissue biopsy.
PubMed ID
18729067 View in PubMed
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Enhanced Abeta40 deposition was associated with increased Abeta42-43 in cerebral vasculature with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D).

https://arctichealth.org/en/permalink/ahliterature187365
Source
Ann N Y Acad Sci. 2002 Nov;977:149-54
Publication Type
Article
Date
Nov-2002
Author
K. Ozawa
T. Tomiyama
M L Maat-Schieman
R A Roos
H. Mori
Author Affiliation
Department of Neuroscience, Institute of Gerontology, Osaka City University, 1-4-3 Asahimachi, Abenoku, Osaka 545-8585, Japan.
Source
Ann N Y Acad Sci. 2002 Nov;977:149-54
Date
Nov-2002
Language
English
Publication Type
Article
Keywords
Amyloid beta-Peptides - genetics
Amyloidosis, Familial - genetics - pathology
Animals
COS Cells
Cercopithecus aethiops
Cerebral Hemorrhage - genetics - pathology
Cerebrovascular Circulation - physiology
Humans
Mice
Mutation
Netherlands
Peptide Fragments - genetics
Sweden
Transfection
Abstract
Cerebrovascular deposition of the amyloid beta-protein (Abeta) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders. Such an Abeta vascular deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses, including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular Abeta deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. We analyzed cerebral Abeta deposition in brains with AD and Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) on the basis of two amyloid species of Abeta(40) and Abeta(42/43) using specific monoclonal antibodies. Compared to Abeta deposition in senile plaques, the molecular composition of Abeta was distinguishable, indicating that the Abeta(40) species is the main component for vascular amyloid. Furthermore, we found Abeta(42/43) immunoreactivity was also much increased in amyloid angiopathy of all cases with HCHWA-D. Taken together, amyloid angiopathy in HCHWA-D may share an Abeta(42)-driven deposition mechanism with plaque amyloid, resulting in enhanced Abeta(40) deposition.
PubMed ID
12480745 View in PubMed
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