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Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches

Wilke, C; Pujol-Calderón, F; Barro, C; Stransky, E; Blennow, K; Michalak, Z; Deuschle, C; ... Synofzik, M; + view all (2019) Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches. Clinical Chemistry and Laboratory Medicine , 57 (10) pp. 1556-1564. 10.1515/cclm-2019-0015. Green open access

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Abstract

Background: Phosphorylated neurofilament heavy (pNfH), a neuronal cytoskeleton protein, might provide a promising blood biomarker of neuronal damage in neurodegenerative diseases (NDDs). The best analytical approaches to measure pNfH levels and whether serum levels correlate with cerebrospinal fluid (CSF) levels in NDDs remain to be determined. / Methods: We here compared analytical sensitivity and reliability of three novel analytical approaches (homebrew Simoa, commercial Simoa and ELISA) for quantifying pNfH in both CSF and serum in samples of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and control subjects. / Results: While all three assays showed highly correlated CSF measurements, Simoa assays also yielded high between-assay correlations for serum measurements (ϱ = 0.95). Serum levels also correlated strongly with CSF levels for Simoa-based measurements (both ϱ = 0.62). All three assays allowed distinguishing ALS from controls by increased CSF pNfH levels, and Simoa assays also by increased serum pNfH levels. pNfH levels were also increased in FTD. / Conclusions: pNfH concentrations in CSF and, if measured by Simoa assays, in blood might provide a sensitive and reliable biomarker of neuronal damage, with good between-assay correlations. Serum pNfH levels measured by Simoa assays closely reflect CSF levels, rendering serum pNfH an easily accessible blood biomarker of neuronal damage in NDDs.

Type: Article
Title: Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1515/cclm-2019-0015
Publisher version: https://doi.org/10.1515/cclm-2019-0015
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: amyotrophic lateral sclerosis (ALS), cerebrospinal fluid (CSF), frontotemporal dementia (FTD), phosphorylated neurofilament heavy chain (pNfH), serum, single molecule array (Simoa)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10079463
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