About this item:

551 Views | 0 Downloads

Author Notes:

Correspondence: Jonathan D. Glass, Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322. Email: jglas03@emory.edu.

Junmin Peng, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322. Email: jpeng@emory.edu.

Jian-Ying Zhou and Leila Afjehi-Sadat share equally in the production of this work.

Junmin Peng and Jonathan D. Glass contribute equally to this work.

We thank Drs. A. Levey, P. Xu and N. T. Seyfried for valuable comments regarding the manuscript, Matt Jaffa for assistance with CSF samples, and Dr. Marla Gearing and Deborah Cooper for providing the human spinal cord tissues.

We also thank Dr. R. Cummings for providing purified Gal3 proteins.

Importantly, we thank the patients and families who contributed tissues and CSF samples, without which this kind of research could not be accomplished.


Research Funding:

This work was supported by the National Institutes of Health grants (P50AG025688, R21NS060182, and P30NS055077) and the Amyotrophic Lateral Sclerosis Association.


  • Motor neuron disease
  • Galectin-3
  • human
  • biomarkers

Galectin-3 Is a Candidate Biomarker for Amyotrophic Lateral Sclerosis: Discovery by a Proteomics Approach


Journal Title:

Journal of Proteome Research


Volume 9, Number 10


, Pages 5133-5141

Type of Work:

Article | Post-print: After Peer Review


The discovery of biomarkers for neurodegenerative diseases will have a major impact on the efficiency of therapeutic clinical trials, and may be important for understanding basic pathogenic mechanisms. We have approached the discovery of protein biomarkers for amyotrophic lateral sclerosis (ALS) by profiling affected tissues in a relevant animal model, and then validating the findings in human tissues. Ventral roots from SOD1G93A “ALS” mice were analyzed by label-free quantitative mass spectrometry, and the resulting data were compared with matched samples from non-transgenic littermates and transgenic mice carrying wild-type human SOD1 (SOD1WT). Out of 1299 proteins, statistical inference of the data in the three groups identified 14 proteins that were dramatically altered in the ALS mice compared with the two control groups. The protein galectin-3 emerged as a lead biomarker candidate based on its differential expression as assessed by immunoblot and immunocytochemistry in SOD1G93A mice as compared to controls, and because it is a secreted protein that could potentially be measured in human biofluids. Spinal cord tissue from ALS patients also showed increased levels of galectin-3 when compared to controls. Further measurement of galectin-3 in cerebrospinal fluid samples showed that ALS patients had approximately twice as much galectin-3 as normal and disease controls. These results provide the proof of principle that biomarker identification in relevant and well-controlled animal models can be translated to human disease. The challenge is to validate our biomarker candidate proteins as true biomarkers for ALS that will be useful for diagnosis and/or monitoring disease activity in future clinical trials.

Copyright information:

© 2010 American Chemical Society

Export to EndNote