Serum Nogo-A levels are not elevated in amyotrophic lateral sclerosis patients

Abstract

Improved biomarkers would facilitate the diagnosis and treatment of amyotrophic lateral sclerosis (ALS). Muscle content of the neuritic outgrowth inhibitor Nogo-A is increased in patients with ALS and other denervating conditions. Seeking a less invasive diagnostic method, we sought to determine whether or not Nogo increases in the serum of ALS patients. We developed a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) protocol to screen serum samples from 172 ALS patients and 172 healthy controls for Nogo-A immunoreactivity. Unexpectedly, there was a trend toward decreased levels of serum Nogo-A in ALS. Mean serum Nogo-A level in ALS patients was 0.71 nM (95% confidence interval (CI) 0.42–1.00), as opposed to 1.15 nM (95% CI 0.72–1.59) in healthy controls. A significantly larger percentage of healthy control sera (11.0% vs 4.7%) displayed markedly elevated levels of Nogo-A. Additional study is required to determine the factors that lead to elevated Nogo-A levels in a subset of both ALS patients and healthy controls.

Keywords::

• ALS
• Nogo-A
• biomarker
• DELFIA
• ELISA

Acknowledgements

We thank Zhengrong Hao and William C. Sessa for sharing their Nogo-B ELISA protocol, and Galen-Royce-Nagel and Patrick Butsch for assistance in obtaining serum samples. We thank the reviewers for excellent comments and suggestions. This work was supported by grants from the NINDS (K08 NS056212), the Falk Medical Research Trust, and the ALS Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health. N.Y.H. and S.M.S. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All the authors certify that no financial conflicts of interest relative to this manuscript are present.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.