Sporadic inclusion body myositis: possible pathogenesis inferred from biomarkers.
OBJECTIVE
The relevance of proteins that accumulate and aggregate in the muscle fibers of patients with sporadic inclusion body myositis (sIBM) is unknown. Many of these proteins also aggregate in other disorders, including Alzheimer's disease, leading to speculation that sIBM pathogenesis has similarities to neurodegenerative disorders. Our review will discuss current studies on these protein biomarkers and their utility in sIBM diagnosis.


RESULTS
Two 'classical' components of sIBM aggregates (amyloid beta and phospho-tau) have been re-evaluated. Three additional components of aggregates (TDP-43, p62, and LC3) have been identified. The sensitivity and specificity of these biomarkers has been explored. Two studies suggest that TDP-43 may have clinical utility in distinguishing sIBM from other inflammatory myopathies.


CONCLUSIONS
The fact that sIBM muscle accumulates multiple protein aggregates with no single protein appearing in every sIBM patient biopsy suggests that it is not presently possible to place pathogenic blame on any single protein (i.e. amyloid beta or TDP-43). Instead changes in protein homeostasis may lead to the accumulation of different proteins that have a propensity to aggregate in skeletal muscle. Therapies aimed at improving protein homeostasis, instead of targeting a specific protein that may or may not accumulate in all sIBM patients, could be useful future strategies for this devastating and enigmatic disorder.
Weihl
Conrad C
CC
Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, Missouri 63110, USA. weihlc@neuro.wustl.edu
Pestronk
Alan
A
D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000209:etiology / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers