Transthyretin Val122Ile, accumulated Abeta, and inclusion-body myositis aspects in cultured muscle

Neurology. 2003 Jul 22;61(2):257-60. doi: 10.1212/01.wnl.0000071219.85847.4e.

Abstract

Cultured muscle fibers (CMF) from a patient with inclusion-body myositis (IBM) and cardiac amyloidosis associated with the transthyretin (TTR) Val122Ile mutation contained aspects of the IBM phenotype: vacuolation, congophilic inclusions, and clusters of immunocolocalizing amyloid beta-peptide (Abeta) and TTR accumulations. These abnormalities are never present in normal human CMF. These perturbations were greatly increased after Abeta precursor protein gene transfer. The TTR mutation may be a genetic predisposition factor for the patient's IBM.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Amino Acid Substitution*
  • Amyloid / chemistry*
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / biosynthesis
  • Amyloid beta-Protein Precursor / genetics
  • Cell Death
  • Cells, Cultured / chemistry
  • Coloring Agents
  • Congo Red
  • DNA, Complementary / genetics
  • Genes, Dominant
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Lysosomes / ultrastructure
  • Male
  • Microscopy, Fluorescence
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / pathology
  • Mutation, Missense*
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / pathology
  • Prealbumin / analysis
  • Prealbumin / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Vacuoles / ultrastructure

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Coloring Agents
  • DNA, Complementary
  • Prealbumin
  • Recombinant Fusion Proteins
  • Congo Red