Impaired innervation of cultured human muscle overexpressing betaAPP experimentally and genetically: relevance to inclusion-body myopathies

Neuroreport. 1998 Oct 5;9(14):3201-5. doi: 10.1097/00001756-199810050-00013.


To investigate whether abnormally accumulated betaAPP may be responsible for denervation of muscle fibers that are present in hereditary inclusion-body myopathy (h-IBM) and sporadic inclusion-body myositis (s-IBM), we cultured five h-IBM and eight normal muscle biopsies. In eight other experiments, a 3 kb human 751-betaAPP-cDNA was transferred, using adenovirus vector, into cultured normal myotubes immediately after myoblast fusion. In all experiments, cultured muscle fibers were co-cultured with fetal rat spinal cord. Controls had no detectable betaAPP epitopes, whereas betaAPP epitopes were greatly increased in cultured h-IBM muscle and in cultured normal muscle after betaAPP-gene transfer. Innervated normal cultured muscle fibers were continuously contracting and fully cross-striated, and they had acetylcholine receptors (AChRs) and acetylcholinesterase (AChE) accumulated only at the neuromuscular junctions (NMJs). By contrast, both groups of betaAPP-overexpressing cultured muscle fibers were not contracting and not cross-striated; and did not have NJMs containing AChRs and AChE. Our results suggest that over-expression of betaAPP in cultured muscle fibers inhibits their innervation, and that the accumulation of betaAPP in muscle fibers of both h- and s-IBM patients may be responsible for their not becoming or remaining properly innervated or reinnervated, i.e. a 'myogenous-dysinnervation' mechanism.

Publication types

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

MeSH terms

  • Adult
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / genetics*
  • Animals
  • Cells, Cultured
  • Epitopes / analysis
  • Fluorescent Antibody Technique
  • Gene Expression / physiology
  • Humans
  • Inclusion Bodies / chemistry*
  • Middle Aged
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / physiology
  • Muscle, Skeletal / innervation*
  • Myositis / metabolism
  • Neuromuscular Junction / chemistry
  • Neurons / cytology
  • Rats
  • Spinal Cord / cytology


  • Amyloid beta-Peptides
  • Epitopes