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The Journal of Neuroscience, May 13, 2009, 29(19):6132-6141; doi:10.1523/JNEUROSCI.1150-09.2009

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Neurobiology of Disease
Immunization with Amyloid-β Attenuates Inclusion Body Myositis-Like Myopathology and Motor Impairment in a Transgenic Mouse Model

Masashi Kitazawa,^1,3 Vitaly Vasilevko,³ David H. Cribbs,^2,3 and Frank M. LaFerla^1,3

Departments of ¹Neurobiology and Behavior and ²Neurology, and ³Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, California 92697-4545

Correspondence should be addressed to Dr. Frank M. LaFerla, Department of Neurobiology and Behavior, 1109 Gillespie Neuroscience Facility, University of California, Irvine, Irvine, CA 92697-4545. Email: laferla{at}uci.edu

Inclusion body myositis (IBM), the most common muscle disease to afflict the elderly, causes slow but progressive degeneration of skeletal muscle and ultimately paralysis. Hallmark pathological features include T-cell mediated inflammatory infiltrates and aberrant accumulations of proteins, including amyloid-β (Aβ), tau, ubiquitinated-proteins, apolipoprotein E, and -synuclein in skeletal muscle. A large body of work indicates that aberrant Aβ accumulation contributes to the myodegeneration. Here, we investigated whether active immunization to promote clearance of Aβ from affected skeletal muscle fibers mitigates the IBM-like myopathological features as well as motor impairment in a transgenic mouse model. We report that active immunization markedly reduces intracellular Aβ deposits and attenuates the motor impairment compared with untreated mice. Results from our current study indicate that Aβ oligomers contribute to the myopathy process as they were significantly reduced in the affected skeletal muscle from immunized mice. In addition, the anti-Aβ antibodies produced in the immunized mice blocked the toxicity of the Aβ oligomers in vitro, providing a possible key mechanism for the functional recovery. These findings provide support for the hypothesis that Aβ is one of the key pathogenic components in IBM pathology and subsequent skeletal muscle degeneration.

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Received March 9, 2009; accepted April 8, 2009.

Correspondence should be addressed to Dr. Frank M. LaFerla, Department of Neurobiology and Behavior, 1109 Gillespie Neuroscience Facility, University of California, Irvine, Irvine, CA 92697-4545. Email: laferla{at}uci.edu

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