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beta-Amyloid precursor protein mRNA is increased in inclusion-body myositis muscle
E Sarkozi1, V Askanas, S A Johnson
1Department of Neurology, University of Southern California, School of Medicine, Los Angeles 90017.
Abstract:
Vacuolated muscle fibers in muscle biopsies of 8 out of 8 inclusion body myositis (IBM) patients, including 2 hereditary patients, manifested increased mRNA for the beta-amyloid precursor protein (beta APP) that contains Kunitz-type protease inhibitor motif. In affected fibers, increased beta APP-mRNA correspond to abnormally accumulated beta APP immunoreactivity (including beta-amyloid protein epitope). In normal human muscle fibers increased beta APP-mRNA was present only at the neuromuscular junctions. Our study (a) suggests that abnormally accumulated beta APP in IBM vacuolated fibers results, at least partly, from increased beta APP generation, and (b) provides the first demonstration of up-regulated beta APP-mRNA in pathologic human tissue other than brain of Alzheimer's disease and Down's syndrome.
Insights
Inclusion body myositis (IBM) muscle fibers show increased beta-amyloid precursor protein (beta APP) mRNA and protein. This suggests higher beta APP production contributes to IBM pathology, a finding previously seen only in brain diseases.
Area of Science:
- Neurology
- Molecular Biology
- Muscle Diseases
Background:
- Inclusion body myositis (IBM) is a progressive muscle-weakening disease.
- The beta-amyloid precursor protein (beta APP) is implicated in neurodegenerative diseases like Alzheimer's.
- The role of beta APP in IBM has not been fully elucidated.
Purpose of the Study:
- To investigate the expression of beta-amyloid precursor protein (beta APP) mRNA and protein in muscle biopsies from IBM patients.
- To determine if increased beta APP generation contributes to the pathology of IBM.
Main Methods:
- Analysis of muscle biopsies from 8 IBM patients (including 2 hereditary cases) and normal controls.
- Quantitative assessment of beta APP mRNA levels using in situ hybridization.
- Immunohistochemical detection of beta APP and beta-amyloid protein epitopes.
Main Results:
- All 8 IBM patients exhibited increased beta APP mRNA in vacuolated muscle fibers.
- Increased beta APP mRNA correlated with abnormal beta APP accumulation and beta-amyloid epitopes in affected fibers.
- In normal muscle, beta APP mRNA was localized to neuromuscular junctions.
Conclusions:
- Abnormal accumulation of beta APP in IBM vacuolated fibers is partly due to increased beta APP generation.
- This study demonstrates up-regulated beta APP mRNA in pathological human muscle tissue, extending findings beyond brain diseases like Alzheimer's.