Linked Life Data

20711838

Source:http://linkedlifedata.com/resource/pubmed/id/20711838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-15
pubmed:abstractText
Accumulation of amyloid-? (A?) within muscle fibers has been considered an upstream step in the development of the s-IBM pathologic phenotype. A?42, which is considered more cytotoxic than A?40 and has a higher propensity to oligomerize, is preferentially increased in s-IBM muscle fibers. In Alzheimer disease (AD), low-molecular weight A? oligomers and toxic oligomers, also referred to as "A?-Derived Diffusible Ligands" (ADDLs), are considered strongly cytotoxic and proposed to play an important pathogenic role. ADDLs have been shown to be increased in AD brain. We now report for the first time that in s-IBM muscle biopsies A?-dimer, -trimer, and -tetramer are identifiable by immunoblots. While all the s-IBM samples we studied had A?-oligomers, their molecular weights and intensity varied between the patient samples. None of the control muscle biopsies had A? oligomers. Dot-immunoblots using highly specific anti-ADDL monoclonal antibodies also showed highly increased ADDLs in all s-IBM biopsies studied, while controls were negative. By immunofluorescence, in some of the abnormal s-IBM muscle fibers ADDLs were accumulated in the form of plaque-like inclusions, and were often increased diffusely in very small fibers. Normal and disease-controls were negative. By gold-immuno-electron microscopy, ADDL-immunoreactivities were in close proximity to 6-10 nm amyloid-like fibrils, and also were immunodecorating amorphous and floccular material. In cultured human muscle fibers, we found that inhibition of autophagy led to the accumulation of A? oligomers. This novel demonstration of A?42 oligomers in s-IBM muscle biopsy provides additional evidence that intra-muscle fiber accumulation of A?42 oligomers in s-IBM may contribute importantly to s-IBM pathogenic cascade.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1432-0533
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
661-6
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Novel demonstration of amyloid-? oligomers in sporadic inclusion-body myositis muscle fibers.
pubmed:affiliation
Department of Neurology, USC Neuromuscular Center, Good Samaritan Hospital, University of Southern California Keck School of Medicine, Los Angeles, CA 90017-1912, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural