title: Effects of nonsteroidal anti-inflammatory drugs on amyloid-beta pathology in mouse skeletal muscle.
abstract: Sporadic inclusion body myositis (sIBM) is a common age-related inflammatory myopathy characterized by the presence of intracellular inclusions that contain the amyloid-beta (Abeta) peptide, a derivative of the amyloid precursor protein (APP). Abeta is believed to cause Alzheimer's disease (AD), suggesting that a link may exist between the two diseases. If AD and sIBM are linked, then treatments that lower Abeta in brain may prove useful for sIBM. To test this hypothesis, transgenic mice that overexpress APP in skeletal muscle were treated for 6 months with a variety of nonsteroidal anti-inflammatory drugs (NSAIDs; naproxen, ibuprofen, carprofen or R-flurbiprofen), a subset of which reduce Abeta in brain and cultured cells. Only ibuprofen lowered Abeta in muscle, and this was not accompanied by corresponding improvements in phenotype. These results indicate that the effects of NSAIDs in the brain may be different from other tissues and that Abeta alone cannot account for skeletal muscle dysfunction in these mice.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.forename: Dana M
authors.initials: DM
authors.lastname: Niedowicz
authors.forename: Christa M
authors.initials: CM
authors.lastname: Studzinski
authors.forename: Adam M
authors.initials: AM
authors.lastname: Weidner
authors.forename: Robin L
authors.initials: RL
authors.lastname: Webb
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Holler
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Ahmed
authors.forename: Harry
authors.initials: H
authors.lastname: LeVine
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal