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标题：Inclusion body myositis-like phenotype induced by transgenic overexpression of βAPP in skeletal muscle
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作者：Michael C. Sugarman ; Tritia R. Yamasaki ; Salvatore Oddo 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：9
页码：6334-6339
DOI：10.1073/pnas.082545599
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Inclusion 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 ({beta}APP), 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 {beta}APP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted {beta}APP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to {beta}APP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of {beta}APP 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 {beta}APP mismetabolism in human IBM.