pNfH is a promising biomarker for ALS

Jeban Ganesalingam, Jiyan An, Robert Bowser, Peter M. Andersen, Christopher E. Shaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median n = 2787 pg/ml, n = 150), compared to headache and other benign controls (3 (4 pg/ml, n = 100, p = <0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (27 (pg/ml for n = 20) which was also highly significant (p = <0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2) = 0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.

Original languageEnglish
Article numberN/A
Pages (from-to)146-149
Number of pages4
JournalAmyotrophic Lateral Sclerosis (United Kingdom)
Volume14
Issue number2
DOIs
Publication statusPublished - Mar 2013

Keywords

  • Neurofilament heavy chain
  • biomarker
  • amyotrophic lateral sclerosis
  • NEUROFILAMENT HEAVY-CHAIN
  • MOTOR-NEURON DISEASE
  • PHOSPHORYLATION
  • DIAGNOSIS
  • ELISA

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