Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep 15:16:173.
doi: 10.1186/s12883-016-0689-x.

Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis

Affiliations

Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis

Xueping Chen et al. BMC Neurol. .

Abstract

Background: The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS).

Methods: Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA.

Results: Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %.

Conclusions: Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

Keywords: Amyotrophic lateral sclerosis; Biomarker; CHIT; S100-β; cystatin C; pNfH.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Scatter plot of levels of pNfH, S100-β, cystatin C, and CHIT in CSF in patients with sporadic ALS and control patients with non-ALS neurological disorders. *the difference is significant
Fig. 2
Fig. 2
Receiver operating curve (ROC) analysis

References

    1. Varghese AM, Sharma A, Mishra P, Vijayalakshmi K, Harsha HC, Sathyaprabha TN, Bharath SM, Nalini A, Alladi PA, Raju TR. Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis. Clin Proteomics. 2013;10(1):19. doi: 10.1186/1559-0275-10-19. - DOI - PMC - PubMed
    1. Pagliardini V, Pagliardini S, Corrado L, Lucenti A, Panigati L, Bersano E, Servo S, Cantello R, D'Alfonso S, Mazzini L. Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study. J Neurol Sci. 2015;348(1–2):245–50. doi: 10.1016/j.jns.2014.12.016. - DOI - PubMed
    1. Brettschneider J, Petzold A, Sussmuth SD, Ludolph AC, Tumani H. Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology. 2006;66(6):852–6. doi: 10.1212/01.wnl.0000203120.85850.54. - DOI - PubMed
    1. Reijn TS, Abdo WF, Schelhaas HJ, Verbeek MM. CSF neurofilament protein analysis in the differential diagnosis of ALS. J Neurol. 2009;256(4):615–9. doi: 10.1007/s00415-009-0131-z. - DOI - PubMed
    1. Ganesalingam J, An J, Bowser R, Andersen PM, Shaw CE. pNfH is a promising biomarker for ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(2):146–9. doi: 10.3109/21678421.2012.729596. - DOI - PubMed

MeSH terms

Supplementary concepts