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Amyotroph Lateral Scler Frontotemporal Degener. 2013 Mar;14(2):146-9. doi: 10.3109/21678421.2012.729596. Epub 2012 Oct 22.

pNfH is a promising biomarker for ALS.

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1
King's Health Partners Centre for Neurodegeneration Research, Institute of Psychiatry, Kings College London, UK.

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 = 2787 pg/ml, n = 150), compared to headache and other benign controls (394 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 (279 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.

PMID:
23134506
DOI:
10.3109/21678421.2012.729596
[Indexed for MEDLINE]
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