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Biomarkers in amyotrophic lateral sclerosis: opportunities and limitations

Insights into the mechanisms of amyotrophic lateral sclerosis (ALS) have relied predominantly on the study of postmortem tissue. Modern technology has improved the ability of scientists to probe effectively the underlying biology of ALS by examination of genomic, proteomic and physiological changes in patients, as well as to monitor functional and structural changes in patients over the course of disease. While effective treatments for ALS are lacking, the discovery of biomarkers for this disease offers clinicians tools for rapid diagnosis, improved ways to monitor disease progression, and insights into the pathophysiology of sporadic ALS. The ultimate aim is to broaden the therapeutic options for patients with this disease.

Key Points

  • Amyotrophic lateral sclerosis (ALS) is characteristically heterogeneous in site of onset, pattern and rate of disease progression

  • Candidate protein-based biomarkers have been identified in the blood and/or cerebrospinal fluid of patients with ALS; assessment of combinations of these biomarkers could improve diagnosis or increase prognostic ability

  • Physiologic biomarkers, including motor unit number estimation and electrical impedance myography, may provide the means to improve monitoring of disease progression in individual patients

  • Advanced MRI techniques have high sensitivity and specificity for detecting ALS at group level, and along with PET can provide mechanistic insights into disease pathogenesis

  • Further studies on large numbers of patients, with longitudinal follow-up, are necessary to validate reported ALS biomarkers

  • The clinical utility of the biomarkers may require a combination of proteomic, physiological and imaging-based methodologies

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R. Bowser, M. R. Turner and J. Shefner contributed equally to researching data for the article, providing substantial contribution to discussion of the content, writing the article, and to review and/or editing of the manuscript before submission.

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Correspondence to Robert Bowser.

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R. Bowser is a stock holder and patent holder with Knopp Biosciences. The other authors declare no competing interests.

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Bowser, R., Turner, M. & Shefner, J. Biomarkers in amyotrophic lateral sclerosis: opportunities and limitations. Nat Rev Neurol 7, 631–638 (2011). https://doi.org/10.1038/nrneurol.2011.151

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