Effects of nonsteroidal anti-inflammatory drugs on amyloid-β pathology in mouse skeletal muscle

Tina L. Beckett; Dana M. Niedowicz; Christa M. Studzinski; Adam M. Weidner; Robin L. Webb; Christopher J. Holler; Rachel R. Ahmed; Harry LeVine; M. Paul Murphy

doi:10.1016/j.nbd.2010.05.018

Effects of nonsteroidal anti-inflammatory drugs on amyloid-β pathology in mouse skeletal muscle

Tina L. Beckett
, Dana M. Niedowicz
, Christa M. Studzinski
, Adam M. Weidner
, Robin L. Webb
, Christopher J. Holler
, Rachel R. Ahmed
, Harry LeVine
, M. Paul Murphy

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Sporadic inclusion body myositis (sIBM) is a common age-related inflammatory myopathy characterized by the presence of intracellular inclusions that contain the amyloid-β (Aβ) peptide, a derivative of the amyloid precursor protein (APP). Aβ 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 Aβ 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 Aβ in brain and cultured cells. Only ibuprofen lowered Aβ 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 Aβ alone cannot account for skeletal muscle dysfunction in these mice.

Original language	English
Pages (from-to)	449-456
Number of pages	8
Journal	Neurobiology of Disease
Volume	39
Issue number	3
DOIs	https://doi.org/10.1016/j.nbd.2010.05.018
State	Published - Sep 2010

Bibliographical note

Funding Information:
Funding was provided by the NIH ( NS058382 , AG005119 , RR020171 , and HL086341 ) and the Myositis Association . All work was approved by the University of Kentucky IACUC. Thanks to Ela Patel (University of Kentucky) for assistance with the histology and Dr. Elizabeth Head (University of Kentucky) for helpful discussion. Additional thanks to Dr. Todd Golde (Mayo Clinic Jacksonville) for providing antibodies and Dr. Frank M. LaFerla (University of California at Irvine) for providing the T7A6 mouse line.

Funding

Funding was provided by the NIH ( NS058382 , AG005119 , RR020171 , and HL086341 ) and the Myositis Association . All work was approved by the University of Kentucky IACUC. Thanks to Ela Patel (University of Kentucky) for assistance with the histology and Dr. Elizabeth Head (University of Kentucky) for helpful discussion. Additional thanks to Dr. Todd Golde (Mayo Clinic Jacksonville) for providing antibodies and Dr. Frank M. LaFerla (University of California at Irvine) for providing the T7A6 mouse line.

Funders	Funder number
National Institutes of Health (NIH)	NS058382, RR020171, HL086341
National Institute on Aging	P01AG005119
Myositis Association

Keywords

Alzheimer's disease
Amyloid
Amyloid-β precursor protein
Inflammation
Sporadic inclusion body myositis

ASJC Scopus subject areas

Neurology

Access to Document

10.1016/j.nbd.2010.05.018

Cite this

@article{ccf020ccc6864f2a8437289a9524b814,

title = "Effects of nonsteroidal anti-inflammatory drugs on amyloid-β 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-β (Aβ) peptide, a derivative of the amyloid precursor protein (APP). Aβ 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 Aβ 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 Aβ in brain and cultured cells. Only ibuprofen lowered Aβ 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 Aβ alone cannot account for skeletal muscle dysfunction in these mice.",

keywords = "Alzheimer's disease, Amyloid, Amyloid-β precursor protein, Inflammation, Sporadic inclusion body myositis",

author = "Beckett, \{Tina L.\} and Niedowicz, \{Dana M.\} and Studzinski, \{Christa M.\} and Weidner, \{Adam M.\} and Webb, \{Robin L.\} and Holler, \{Christopher J.\} and Ahmed, \{Rachel R.\} and Harry LeVine and Murphy, \{M. Paul\}",

note = "Funding Information: Funding was provided by the NIH ( NS058382 , AG005119 , RR020171 , and HL086341 ) and the Myositis Association . All work was approved by the University of Kentucky IACUC. Thanks to Ela Patel (University of Kentucky) for assistance with the histology and Dr. Elizabeth Head (University of Kentucky) for helpful discussion. Additional thanks to Dr. Todd Golde (Mayo Clinic Jacksonville) for providing antibodies and Dr. Frank M. LaFerla (University of California at Irvine) for providing the T7A6 mouse line.",

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language = "English",

volume = "39",

pages = "449--456",

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AU - Webb, Robin L.

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AU - Ahmed, Rachel R.

AU - LeVine, Harry

AU - Murphy, M. Paul

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PY - 2010/9

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N2 - Sporadic inclusion body myositis (sIBM) is a common age-related inflammatory myopathy characterized by the presence of intracellular inclusions that contain the amyloid-β (Aβ) peptide, a derivative of the amyloid precursor protein (APP). Aβ 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 Aβ 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 Aβ in brain and cultured cells. Only ibuprofen lowered Aβ 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 Aβ alone cannot account for skeletal muscle dysfunction in these mice.

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Effects of nonsteroidal anti-inflammatory drugs on amyloid-β pathology in mouse skeletal muscle

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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