Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis.
In 11 of 11 inclusion-body myositis (IBM) patients, including one hereditary case, vacuolated muscle fibers contained large and multiple small inclusions immunoreactive for beta-amyloid protein (beta AP). All IBM muscle biopsies had characteristic cytoplasmic tubulo-filaments (CTFs) by electron microscopy. None of 14 control muscle biopsies contained the beta AP immunoreactive (IR) inclusions characteristic of IBM. On the light microscopy level, beta AP-IR inclusions colocalized with ubiquitin immunoreactivity. By immunogold electronmicroscopy, beta AP immunoreactivity was localized to a) amorphous, poorly defined structures, b) dense floccular material, c) clusters of loosely packed amyloidlike fibrils 6-8 nm in diameter, and d) poorly defined loose fibrillar structures 6-8 nm in diameter. beta AP immunoreactive structures were often in proximity to CTFs, but CTFs themselves never contained beta AP-IR. Our study provides the first demonstration of beta AP accumulations in abnormal human muscle. This finding suggests that in addition to Alzheimer's disease, Down syndrome, and Dutch-type hereditary cerebrovascular amyloidosis, beta AP may play an important role in the pathogenesis of other diseases, including ones outside the central nervous system, for example, IBM.
Askanas
V
V
University of Southern California Neuromuscular Center, Los Angeles 90017.
Engel
W K
WK
Alvarez
R B
RB
D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000293:Adolescent; D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000378:metabolism; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008875:Middle Aged; D009132:Muscles / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D009220:Myositis / Q000378:metabolism / Q000473:pathology*
D016229:Amyloid beta-Peptides