Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.

TitleInclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.
Publication TypeJournal Article
Year of Publication2002
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue9
Pagination6334-9
Date Published2002 Apr 30
ISSN0027-8424
AbstractInclusion body myositis (IBM), the most common age-related muscle disease in the elderly population, is an incurable disorder leading to severe disability. Sporadic IBM has an unknown etiology, although affected muscle fibers are characterized by many of the pathobiochemical alterations traditionally associated with neurodegenerative brain disorders such as Alzheimer's disease. Accumulation of the amyloid-beta peptide, which is derived from proteolysis of the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and also in IBM, where in the latter, it predominantly occurs intracellularly within affected myofibers. To elucidate the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted betaAPP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of betaAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance. These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM.
URLhttp://www.pnas.org/cgi/pmidlookup?view=long&pmid=11972038
DOI10.1073/pnas.082545599
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/11972038?dopt=Abstract
Short TitleProc Natl Acad Sci U S A