title: pNfH is a promising biomarker for ALS.
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.
authors.affiliation: King's Health Partners Centre for Neurodegeneration Research, Institute of Psychiatry, Kings College London, UK.
authors.forename: Jeban
authors.initials: J
authors.lastname: Ganesalingam
authors.forename: Jiyan
authors.initials: J
authors.lastname: An
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Shaw
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D015995:Prevalence; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H