Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 93; no. 1; pp. 68 - 74
• Main Authors: Halbgebauer, Steffen, Steinacker, Petra, Verde, Federico, Weishaupt, Jochen, Oeckl, Patrick, von Arnim, Christine, Dorst, Johannes, Feneberg, Emily, Mayer, Benjamin, Rosenbohm, Angela, Silani, Vincenzo, Ludolph, Albert C, Otto, Markus
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.01.2022; BMJ Publishing Group LTD
• Subjects: Adult; Aged; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Cohort Studies; Creutzfeldt-Jakob disease; Diagnosis, Differential; Female; Frontotemporal Dementia - diagnosis; Humans; Intermediate Filaments; Male; Medical diagnosis; Middle Aged; Neurodegeneration; Neurofilament Proteins - blood; Neurofilament Proteins - cerebrospinal fluid; Parkinson's disease; ROC Curve; United States > US; Germany
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2021-327129

ObjectiveElevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential.MethodsIn total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer’s disease (n=20), Parkinson’s disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD).ResultsCSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94).ConclusionOur results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.