| First Author | Sugarman MC | Year | 2006 |
| Journal | Neurobiol Aging | Volume | 27 |
| Issue | 3 | Pages | 423-32 |
| PubMed ID | 15950323 | Mgi Jnum | J:105441 |
| Mgi Id | MGI:3615080 | Doi | 10.1016/j.neurobiolaging.2005.02.011 |
| Citation | Sugarman MC, et al. (2006) Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic model. Neurobiol Aging 27(3):423-32 |
| abstractText | Inclusion body myositis (IBM) is the most common age-related degenerative skeletal muscle disorder. The aberrant intracellular accumulation of the beta-amyloid (Abeta) peptide within skeletal muscle is a pathological hallmark of IBM. Skeletal muscle is comprised of both slow and fast twitch fibers, which are present in different proportions in various muscles. It remains unclear if fast and/or slow twitch fibers are differentially involved in IBM pathogenesis. To better understand the molecular pathogenesis of IBM, we analyzed human IBM muscle biopsies and muscle from a transgenic mouse model of IBM (MCK-betaAPP). Here we report that the majority of histopathologically-affected fibers in human IBM biopsies were type II fast fibers. Skeletal muscle from MCK-betaAPP mice exhibited higher transgene expression and steady-state levels of human betaAPP in fast type IIB fibers compared to slow type I fibers. These findings indicate that fast twitch fibers may selectively accumulate and be more vulnerable to betaAPP- and Abeta-mediated damage in IBM. These findings also highlight parallels between the MCK-betaAPP mice and the human IBM condition. |
