Dataset Information

Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy.

ABSTRACT: Molecular chaperones, including the extracellular protein clusterin (CLU), play a significant role in maintaining proteostasis; they have a unique capacity to bind and stabilize non-native protein conformations, prevent aggregation, and keep proteins in a soluble folding-competent state. In this study, we investigated amyloid-infiltrated cardiac tissue for the presence of CLU and measured serum levels of CLU in patients with and without amyloidotic cardiomyopathy (CMP). Cardiac tissues containing amyloid deposits composed of either transthyretin (TTR) or Ig light chain from nine patients with amyloidotic CMP were examined for the presence of CLU using immunohistochemical techniques. CLU staining coincided with the extracellular myocardial amyloid deposits in tissues from patients with familial TTR, senile systemic, and Ig light chain amyloidosis. The association of CLU with cardiac amyloid deposits was confirmed by immunogold electron microscopy. Serum concentrations of CLU were measured in familial TTR, senile systemic, and Ig light chain amyloidosis patient groups and compared with both age-matched healthy controls and with patients with CMP unrelated to amyloid disease. Subset analysis of disease cohorts, based on cardiac involvement, indicated that decreased serum CLU concentrations were associated with amyloidotic CMP. Taken together, these results suggest that CLU may play a pathogenetic role in TTR and Ig light chain amyloidoses and amyloidotic CMP.

SUBMITTER: Greene MJ

PROVIDER: S-EPMC3070592 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy.

Greene Michael J MJ Sam Flora F Soo Hoo Pamela T PT Patel Rupesh S RS Seldin David C DC Connors Lawreen H LH

The American journal of pathology 20101223 1

Molecular chaperones, including the extracellular protein clusterin (CLU), play a significant role in maintaining proteostasis; they have a unique capacity to bind and stabilize non-native protein conformations, prevent aggregation, and keep proteins in a soluble folding-competent state. In this study, we investigated amyloid-infiltrated cardiac tissue for the presence of CLU and measured serum levels of CLU in patients with and without amyloidotic cardiomyopathy (CMP). Cardiac tissues containin ...[more]

PMID: 21224044

Similar Datasets

Project description:Converging evidence indicates that clusterin, a chaperone glycoprotein, influences Alzheimer disease neurodegeneration. However, the precise role of clusterin in Alzheimer disease pathogenesis is still not well understood.To elucidate the relationship between clusterin, amyloid-? (A?), phosphorylated tau (p-tau), and the rate of brain atrophy over time among nondemented older individuals.This longitudinal cohort included cognitively normal older participants and individuals with mild cognitive impairment assessed with baseline lumbar puncture and longitudinal structural magnetic resonance imaging. We examined 241 nondemented older individuals from research centers across the United States and Canada (91 participants with a Clinical Dementia Rating score of 0 and 150 individuals with a Clinical Dementia Rating score of 0.5).Using linear mixed-effects models, we investigated interactions between cerebrospinal fluid (CSF) clusterin, CSF A?1-42, and CSF p-tau at threonine 181 (p-tau181p) on the atrophy rate of the entorhinal cortex and hippocampus.Across all participants, we found a significant interaction between CSF clusterin and CSF A?1-42 on the entorhinal cortex atrophy rate but not on the hippocampal atrophy rate. Cerebrospinal fluid clusterin was associated with the entorhinal cortex atrophy rate among CSF A?1-42-positive individuals but not among CSF A?1-42-negative individuals. In secondary analyses, we found significant interactions between CSF A?1-42 and CSF clusterin, as well as CSF A?1-42 and CSF p-tau181p, on the entorhinal cortex atrophy rate. We found similar results in subgroup analyses within the mild cognitive impairment and cognitively normal cohorts.In nondemented older individuals, A?-associated volume loss occurs in the presence of elevated clusterin. The effect of clusterin on A?-associated brain atrophy is not confounded or explained by p-tau. These findings implicate a potentially important role for clusterin in the earliest stages of the Alzheimer disease neurodegenerative process and suggest independent effects of clusterin and p-tau on A?-associated volume loss.

Dataset Information

Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy.

Publications

Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets